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All around us there is an invisible world. | 0:00:03 | 0:00:06 | |
The microscopic world of bacteria. | 0:00:12 | 0:00:16 | |
Some of these bacteria are going rogue, | 0:00:19 | 0:00:21 | |
becoming superbugs that we can't control. | 0:00:21 | 0:00:26 | |
They're probably smarter than I am. | 0:00:29 | 0:00:31 | |
They're able to adjust fire much quicker than me | 0:00:31 | 0:00:33 | |
so they're able to develop resistance a whole lot faster | 0:00:33 | 0:00:36 | |
than I can develop an antibiotic. | 0:00:36 | 0:00:37 | |
Antibiotics are one of the miracles of modern medicine | 0:00:41 | 0:00:44 | |
and scientists now worry that superbugs are emerging | 0:00:46 | 0:00:49 | |
which are becoming totally resistant to these drugs. | 0:00:49 | 0:00:53 | |
That's the scary day, that's the day when for some unlucky person | 0:00:53 | 0:00:58 | |
their day has come, right, that the drugs no longer work. | 0:00:58 | 0:01:03 | |
But researchers are engaged in a fight-back against the superbugs. | 0:01:07 | 0:01:12 | |
Bacteria have been on the earth for billion years, | 0:01:13 | 0:01:16 | |
humans have been on the earth a few hundred thousand years. | 0:01:16 | 0:01:20 | |
Right so, they have the accumulated smarts of eons of generations. | 0:01:20 | 0:01:25 | |
What we do have, as humans, is we have brains. | 0:01:25 | 0:01:28 | |
The rise of bacteria resistant to antibiotics | 0:01:30 | 0:01:34 | |
is being seen as a major public health threat. | 0:01:34 | 0:01:38 | |
So scientists are devising new and sophisticated ways | 0:01:41 | 0:01:45 | |
to try to defeat the superbugs. | 0:01:45 | 0:01:47 | |
Professor Hazel Barton is tracking down | 0:02:09 | 0:02:13 | |
one of humanity's greatest treasures. | 0:02:13 | 0:02:15 | |
To find it she has to venture | 0:02:21 | 0:02:23 | |
to one of the most untouched places on earth, | 0:02:23 | 0:02:26 | |
hundreds of metres underground. | 0:02:27 | 0:02:31 | |
It's finding a hole, nobody knows where it goes | 0:02:31 | 0:02:35 | |
and you kind of push and shove your way through, | 0:02:35 | 0:02:37 | |
and it's spectacular and it's beautiful | 0:02:37 | 0:02:39 | |
and you're the first person to see it and you leave the first footprints. | 0:02:39 | 0:02:43 | |
And so you get kind of a man in the moon feeling to be in there. | 0:02:47 | 0:02:50 | |
She's hunting for something that we all take for granted. | 0:02:54 | 0:02:58 | |
In these caves are tiny microbes crucial to our survival. | 0:03:00 | 0:03:05 | |
Where you want to go is where you can spot bedrock | 0:03:07 | 0:03:12 | |
and it's kind of dry but near enough the water that | 0:03:12 | 0:03:15 | |
that organic material can leach in. | 0:03:15 | 0:03:18 | |
And so somewhere like here, and you can see, this is one here. | 0:03:18 | 0:03:23 | |
These little dots of white here are the colonies of microbes. | 0:03:23 | 0:03:29 | |
So those are what we go in for and those are what we go after. | 0:03:29 | 0:03:31 | |
These tiny microbes are incredibly precious | 0:03:36 | 0:03:39 | |
because they can produce life-saving drugs we all rely on. | 0:03:39 | 0:03:43 | |
Antibiotics. | 0:03:44 | 0:03:46 | |
Professor Barton is going to the ends of the earth | 0:03:47 | 0:03:51 | |
because here she can find new antibiotics. | 0:03:51 | 0:03:54 | |
We need new ones, because the ones we have are starting to fail. | 0:03:55 | 0:04:01 | |
The last thing you want to do is go to the clinic, give someone | 0:04:01 | 0:04:04 | |
this drug that's gonna save their life, and it's not working. | 0:04:04 | 0:04:07 | |
Scientists like Professor Barton are going to such extreme lengths | 0:04:11 | 0:04:16 | |
because finding new antibiotics is fast becoming | 0:04:16 | 0:04:20 | |
the most critical concern. | 0:04:20 | 0:04:22 | |
Antibiotics are one of the miracles of modern medicine. | 0:04:31 | 0:04:36 | |
Since the discovery of penicillin in 1928, | 0:04:36 | 0:04:40 | |
they have revolutionized our lives. | 0:04:40 | 0:04:42 | |
They have stopped simple cuts | 0:04:48 | 0:04:50 | |
developing into life-threatening infections, | 0:04:50 | 0:04:53 | |
saved millions from diseases like cholera, | 0:04:53 | 0:04:57 | |
diphtheria and tuberculosis. | 0:04:57 | 0:05:00 | |
Antibiotics are so valuable because they stop and destroy | 0:05:02 | 0:05:06 | |
the bacteria that cause these life-threatening diseases. | 0:05:06 | 0:05:10 | |
But over the last decade scientists have witnessed outbreaks | 0:05:12 | 0:05:16 | |
around the world where antibiotics we have relied on in the past | 0:05:16 | 0:05:20 | |
have stopped working. | 0:05:20 | 0:05:22 | |
These outbreaks have been caused by new types of bacteria. | 0:05:23 | 0:05:28 | |
Bacteria that can sweep straight through our antibiotics, | 0:05:28 | 0:05:31 | |
and carry on growing. | 0:05:31 | 0:05:33 | |
These are the superbugs. | 0:05:35 | 0:05:37 | |
And we are becoming powerless against them. | 0:05:40 | 0:05:44 | |
But by studying these outbreaks, | 0:05:44 | 0:05:46 | |
scientists are hoping to defeat them. | 0:05:46 | 0:05:49 | |
The Brooke Army Medical Centre in Texas. | 0:05:54 | 0:05:58 | |
Just a few years ago, this renowned military hospital | 0:06:01 | 0:06:06 | |
unexpectedly found itself at the frontline | 0:06:06 | 0:06:09 | |
of the war against superbugs. | 0:06:09 | 0:06:11 | |
It started in 2006 when Master Sergeant Dan Robles | 0:06:12 | 0:06:17 | |
was just four months into his deployment to Iraq. | 0:06:17 | 0:06:20 | |
His unit was on a routine patrol, searching for a weapons cache. | 0:06:22 | 0:06:26 | |
It was about 2.00 in the afternoon, Baghdad time. | 0:06:32 | 0:06:36 | |
It looked like business as usual, cars driving back and forth, | 0:06:37 | 0:06:41 | |
people on the side of the streets. | 0:06:41 | 0:06:44 | |
It was quiet. | 0:06:44 | 0:06:46 | |
And there was just a big flash of light, | 0:06:50 | 0:06:55 | |
it sounded like I had my head in a bell | 0:06:55 | 0:06:58 | |
and someone was pounding on it real hard. | 0:06:58 | 0:06:59 | |
There was smoke everywhere. | 0:06:59 | 0:07:01 | |
The patrol had been hit by an IED | 0:07:03 | 0:07:06 | |
which tore into his side of the vehicle. | 0:07:06 | 0:07:08 | |
Sitting there in the Humvee after the explosion, I looked down | 0:07:12 | 0:07:15 | |
and I saw that one part of my leg, my calf muscle, | 0:07:15 | 0:07:19 | |
through the pants of my uniform. | 0:07:19 | 0:07:22 | |
And I didn't want to look down after that. | 0:07:22 | 0:07:25 | |
He sustained terrible injuries, | 0:07:28 | 0:07:30 | |
and ultimately the combat medics were unable to save his legs. | 0:07:30 | 0:07:34 | |
Within days, he was back on home soil at the Brooke Army Medical Centre, | 0:07:39 | 0:07:44 | |
but he was about to face an even tougher battle. | 0:07:44 | 0:07:47 | |
His wounds were infected and the usual antibiotics weren't working. | 0:07:51 | 0:07:57 | |
So they called in the Chief of the Infectious Disease Service, | 0:08:03 | 0:08:07 | |
Colonel Clint Murray. | 0:08:07 | 0:08:09 | |
You're not necessarily sure who the enemy is | 0:08:11 | 0:08:13 | |
when you walk in to see your patient. | 0:08:13 | 0:08:15 | |
I think it's very similar to what we do in combat, | 0:08:15 | 0:08:18 | |
is we try to figure out what we're doing who are we fighting? | 0:08:18 | 0:08:21 | |
Why are we fighting them? | 0:08:21 | 0:08:22 | |
Colonel Murray discovered that his patient had brought back from Iraq | 0:08:24 | 0:08:29 | |
three of the toughest superbugs to beat. | 0:08:29 | 0:08:32 | |
The first thing to do was protect the other patients | 0:08:37 | 0:08:41 | |
and control the outbreak. | 0:08:41 | 0:08:44 | |
So what we do is we try to isolate all our patients, | 0:08:44 | 0:08:47 | |
put them in their private rooms and before we go in | 0:08:47 | 0:08:49 | |
and out of those rooms, we put on gowns and gloves | 0:08:49 | 0:08:51 | |
to really prevent the bacteria from getting on us | 0:08:51 | 0:08:53 | |
so when we get to the next patient's room | 0:08:53 | 0:08:55 | |
we're not taking the bacteria with us. | 0:08:55 | 0:08:57 | |
Everyone does this, | 0:08:59 | 0:09:00 | |
so you'll actually see pictures of Presidents putting this stuff on | 0:09:00 | 0:09:03 | |
before they've gone into some soldier's room in the past. | 0:09:03 | 0:09:06 | |
It's just what you do. | 0:09:06 | 0:09:07 | |
Now he turned his attention to treating the infection, | 0:09:11 | 0:09:15 | |
but his usual arsenal of antibiotics just wouldn't work. | 0:09:15 | 0:09:19 | |
The number of antimicrobial agents we had were limited to treat them. | 0:09:20 | 0:09:24 | |
So in contrast to giving them the standard antibiotic | 0:09:24 | 0:09:26 | |
we give anyone that has a wound, we'd have to sort of | 0:09:26 | 0:09:30 | |
what we call is a bigger gun, but a more powerful antibiotic. | 0:09:30 | 0:09:33 | |
But these powerful antibiotics carry a risk. | 0:09:35 | 0:09:38 | |
They're not just toxic to bacteria, they can be toxic to people too. | 0:09:40 | 0:09:45 | |
I do remember Dr Murray explaining my situation to me, | 0:09:46 | 0:09:50 | |
and I was like, "OK, let's do it, whatever we've got to do." | 0:09:50 | 0:09:54 | |
Like most doctors, Colonel Murray has rarely used these antibiotics | 0:09:54 | 0:09:59 | |
because of the damaging side effects. | 0:09:59 | 0:10:02 | |
It had started to shut down my kidneys, I went into renal failure. | 0:10:02 | 0:10:07 | |
And so he comes back and says, "We've got to stop the antibiotics." | 0:10:07 | 0:10:11 | |
Based upon that, I really figured out, OK so here are the bacteria | 0:10:11 | 0:10:15 | |
and here's how we're helping you, but here's how we're hurting you. | 0:10:15 | 0:10:18 | |
I knew it was going to be a long fight | 0:10:18 | 0:10:21 | |
when it started doing more damage than good. | 0:10:21 | 0:10:25 | |
They had to keep changing the antibiotics | 0:10:27 | 0:10:30 | |
as each one became too toxic. | 0:10:30 | 0:10:32 | |
And this time it had shut down my immune system. | 0:10:35 | 0:10:39 | |
That was probably the most scary thing ever, | 0:10:39 | 0:10:43 | |
out of my whole ordeal. | 0:10:43 | 0:10:44 | |
No white blood cells, no immune system. | 0:10:44 | 0:10:49 | |
I had to wear a mask, I was in isolation. | 0:10:49 | 0:10:53 | |
Any cold, any...you know, the simple cold could have killed me | 0:10:53 | 0:10:59 | |
because I had nothing to fight it off. | 0:10:59 | 0:11:01 | |
Dan Robles is living a normal life back with his family, | 0:11:04 | 0:11:08 | |
but six years after the attack he still comes here | 0:11:08 | 0:11:12 | |
to check on his ongoing struggle with the superbugs. | 0:11:12 | 0:11:15 | |
Looking back over the two battles for his life, | 0:11:17 | 0:11:20 | |
his fight with the superbugs was the toughest. | 0:11:20 | 0:11:24 | |
When I was hurt, at least I knew that there was a chance | 0:11:24 | 0:11:27 | |
that I could survive, and that things were in place | 0:11:27 | 0:11:32 | |
to take care of me and fix me and make me better. | 0:11:32 | 0:11:35 | |
But as far as losing your immune system, | 0:11:35 | 0:11:39 | |
there was nothing that any doctor in the hospital could do | 0:11:39 | 0:11:44 | |
to keep me from getting the simple cold that could potentially kill me. | 0:11:44 | 0:11:51 | |
That was the scariest. | 0:11:51 | 0:11:54 | |
And it was scary because my family was right there with me. | 0:11:54 | 0:11:58 | |
And I was more worried about them watching something like that happen | 0:11:58 | 0:12:03 | |
than me coming back from Iraq in a box. | 0:12:03 | 0:12:07 | |
The Brooke Army Medical Centre experienced what happens | 0:12:10 | 0:12:13 | |
when a superbug enters a hospital. | 0:12:13 | 0:12:16 | |
Often the only choice for doctors is to use antibiotics | 0:12:18 | 0:12:22 | |
which themselves can be harmful. | 0:12:22 | 0:12:24 | |
The antibiotics that I could use ten years ago | 0:12:24 | 0:12:26 | |
are almost completely ineffective now | 0:12:26 | 0:12:28 | |
for some of the bacteria we have. | 0:12:28 | 0:12:30 | |
And often times we are resorting | 0:12:30 | 0:12:32 | |
to that last-ditch effort of antibiotics. | 0:12:32 | 0:12:35 | |
If we don't fix this issue, | 0:12:35 | 0:12:37 | |
we're eventually not going to have antibiotics. | 0:12:37 | 0:12:40 | |
The reason scientists are concerned is that over the last ten years, | 0:12:49 | 0:12:53 | |
antibiotic resistance has been growing across the world, | 0:12:53 | 0:12:57 | |
which has forced scientists to devise new strategies to combat it. | 0:12:59 | 0:13:04 | |
Dr Ruth McNerney is at the forefront of the battle against tuberculosis, | 0:13:13 | 0:13:17 | |
a disease caused by bacteria we thought we'd confined to history. | 0:13:17 | 0:13:21 | |
In the 18th-19th century, | 0:13:24 | 0:13:26 | |
tuberculosis was the biggest killer, full stop. | 0:13:26 | 0:13:29 | |
I mean, not just in infectious diseases. | 0:13:29 | 0:13:31 | |
In the middle of the 19th century, life expectancy was just 41. | 0:13:33 | 0:13:37 | |
In this time before antibiotics, | 0:13:39 | 0:13:41 | |
diseases like TB spread through the crowded and cramped streets. | 0:13:41 | 0:13:46 | |
It transmits very easily through the air | 0:13:46 | 0:13:50 | |
so it's very hard to avoid getting TB, | 0:13:50 | 0:13:52 | |
you don't know you've been exposed, | 0:13:52 | 0:13:54 | |
you don't have to do anything to catch TB, except continue breathing. | 0:13:54 | 0:13:57 | |
It would just affect everyone. Young and old. | 0:13:58 | 0:14:02 | |
One of the great achievements of modern medicine | 0:14:05 | 0:14:08 | |
was the defeat of this disease with a cocktail of antibiotics. | 0:14:08 | 0:14:12 | |
Today, over 8 million people live in London | 0:14:14 | 0:14:18 | |
without giving a thought to TB. | 0:14:18 | 0:14:20 | |
But our crowded cities are still the perfect playground for bacteria. | 0:14:23 | 0:14:28 | |
We pour into the city every day, we pour down the tube, | 0:14:28 | 0:14:32 | |
on to buses, out round the streets. | 0:14:32 | 0:14:34 | |
If someone had infectious TB, | 0:14:34 | 0:14:36 | |
and they were coughing out the tiny droplets | 0:14:36 | 0:14:38 | |
then it would be very easy to infect so many people. | 0:14:38 | 0:14:41 | |
It would spread very, very easily. | 0:14:41 | 0:14:42 | |
Now if we can imagine that we didn't have the antibiotics to treat TB, | 0:14:42 | 0:14:46 | |
well, we'd be in big trouble because that's the only way | 0:14:46 | 0:14:49 | |
we can stop TB spreading. | 0:14:49 | 0:14:50 | |
But the fear now is that our achievement | 0:14:52 | 0:14:55 | |
in controlling this disease is being threatened. | 0:14:55 | 0:14:58 | |
Dr McNerney is seeing a rise in cases of antibiotic-resistant TB. | 0:14:59 | 0:15:05 | |
We're now seeing the emergence of strains of TB | 0:15:05 | 0:15:08 | |
that are resistant to the drugs. | 0:15:08 | 0:15:10 | |
And that's becoming quite a serious problem. | 0:15:10 | 0:15:13 | |
One of the issues is that we don't know how much drug resistance | 0:15:13 | 0:15:16 | |
there is because it's actually quite difficult to measure. | 0:15:16 | 0:15:18 | |
For now, the resistant strains showing up in the UK | 0:15:20 | 0:15:24 | |
can still be treated by a small number of antibiotics. | 0:15:24 | 0:15:28 | |
But outside the UK, Dr McNerney has seen a new strain of TB emerge | 0:15:28 | 0:15:33 | |
that is resistant to all of the antibiotics we have to treat it. | 0:15:33 | 0:15:37 | |
It could arrive tomorrow on an aeroplane. It might already be here. | 0:15:37 | 0:15:40 | |
We don't know. We just have to be on our guard. | 0:15:40 | 0:15:43 | |
We just can't afford to let this genie out of the bag. | 0:15:43 | 0:15:47 | |
Scientists are now trying to understand | 0:15:56 | 0:15:59 | |
exactly how superbugs have gained resistance, | 0:15:59 | 0:16:03 | |
and, ultimately, how we can defeat them. | 0:16:05 | 0:16:08 | |
Here at Harvard University, | 0:16:19 | 0:16:23 | |
scientists are investigating why some of our antibiotics are failing. | 0:16:23 | 0:16:26 | |
It's an experiment that happens in Professor Roy Kishony's lab. | 0:16:31 | 0:16:37 | |
Here they are deliberately trying to create superbugs. | 0:16:38 | 0:16:42 | |
This is a new device we've developed - we call it the morbidostat. | 0:16:44 | 0:16:48 | |
Using the morbidostat, they are going to produce a highly resistant version | 0:16:51 | 0:16:56 | |
of a harmless strain of a bacteria we all have in our gut. | 0:16:56 | 0:16:59 | |
E. coli. | 0:16:59 | 0:17:01 | |
At the beginning you have bacteria just growing | 0:17:02 | 0:17:05 | |
happily in the tubes, they have enough food, they are growing fast. | 0:17:05 | 0:17:08 | |
They start by trying to kill the E. coli | 0:17:11 | 0:17:14 | |
by dripping in a low concentration of antibiotic. | 0:17:14 | 0:17:17 | |
But as the millions of bacteria have been multiplying in the tubes, | 0:17:20 | 0:17:24 | |
some, by chance, will have developed mutations | 0:17:24 | 0:17:26 | |
that allow them to be resistant to the antibiotic. | 0:17:26 | 0:17:30 | |
This mutant would start replicating faster than everyone else, | 0:17:30 | 0:17:34 | |
ultimately it would take over on the whole population. | 0:17:34 | 0:17:38 | |
So now they try to kill this new mutant strain. | 0:17:38 | 0:17:42 | |
They up the strength of the antibiotic. | 0:17:43 | 0:17:46 | |
Again, most of them die. | 0:17:46 | 0:17:48 | |
But a new mutation appears, | 0:17:48 | 0:17:52 | |
that can survive the even stronger antibiotic. | 0:17:52 | 0:17:55 | |
And then we see another step, now they can grow | 0:17:55 | 0:17:58 | |
in even higher drug concentrations, | 0:17:58 | 0:18:00 | |
so we keep iterating this process over and over and over. | 0:18:00 | 0:18:04 | |
This experiment shows that bacteria become resistant | 0:18:06 | 0:18:10 | |
by being exposed to low levels of the very thing we use to protect us, | 0:18:10 | 0:18:15 | |
antibiotics. | 0:18:15 | 0:18:18 | |
Now the team have created a new experiment to find out exactly | 0:18:24 | 0:18:28 | |
what is happening in these mutant bacteria to allow them be resistant. | 0:18:28 | 0:18:33 | |
It starts with what is in effect a giant Petri dish. | 0:18:38 | 0:18:42 | |
We're setting an experiment really for the first time | 0:18:44 | 0:18:47 | |
in which we're going to let bacteria swim against | 0:18:47 | 0:18:52 | |
an ever-increasing concentration of an antibiotic, and see what happens. | 0:18:52 | 0:18:56 | |
The jelly contains food for the bacteria to grow, | 0:18:58 | 0:19:01 | |
but each slab is infused with an increasing concentration | 0:19:01 | 0:19:05 | |
of antibiotic, which should act as a barrier, killing the bacteria. | 0:19:05 | 0:19:09 | |
First slab is no drug, | 0:19:10 | 0:19:13 | |
then about the amount needed to kill the bacteria, | 0:19:13 | 0:19:15 | |
then ten times more, 100 times more, and 1,000 times more. | 0:19:15 | 0:19:19 | |
The experiment begins with a tiny drop of E. coli. | 0:19:22 | 0:19:26 | |
They're certainly going to spread when there is no drug but | 0:19:28 | 0:19:31 | |
we want to see can they actually go to the place where there is an antibiotic? | 0:19:31 | 0:19:35 | |
A time-lapse camera captures the spread of the bacteria. | 0:19:37 | 0:19:42 | |
As the experiment begins, it's easy for the bacteria to grow | 0:19:45 | 0:19:49 | |
in the first section, with no antibiotic. | 0:19:49 | 0:19:52 | |
Where there is no drug, it's very easy for them, | 0:19:55 | 0:19:57 | |
there's food but no stress. | 0:19:57 | 0:19:59 | |
Then they hit the boundary where the drug concentration increases. | 0:19:59 | 0:20:03 | |
At the barrier where the antibiotic starts | 0:20:03 | 0:20:06 | |
at the first concentration, the spread is halted. | 0:20:06 | 0:20:10 | |
They get stuck there for a while, | 0:20:10 | 0:20:12 | |
they try to go into this area because there is food, | 0:20:12 | 0:20:15 | |
but every time they try to go into it they get killed by the drug. | 0:20:15 | 0:20:18 | |
But that doesn't last long. | 0:20:21 | 0:20:24 | |
Very soon, a mutant appears that can break through the barrier. | 0:20:24 | 0:20:29 | |
Whole new colonies grow that can live happily | 0:20:29 | 0:20:32 | |
in this concentration of antibiotic. | 0:20:32 | 0:20:34 | |
And it doesn't stop there, this happens again and again, | 0:20:37 | 0:20:43 | |
even up to 1,000 times concentration. | 0:20:43 | 0:20:46 | |
At the end of the experiment we are the maximal level of solubility | 0:20:48 | 0:20:51 | |
of the drug, we just cannot add more drug, it doesn't dissolve anymore. | 0:20:51 | 0:20:56 | |
This carefully controlled epidemic | 0:20:57 | 0:21:00 | |
all happens in the space of just one week. | 0:21:00 | 0:21:03 | |
The team is beginning to pick apart these mutant bacteria | 0:21:04 | 0:21:07 | |
to see exactly how this is happening in the presence of antibiotics, | 0:21:07 | 0:21:12 | |
by peering inside the bacteria, at their genes. | 0:21:13 | 0:21:18 | |
What actually happen under the hood, | 0:21:18 | 0:21:19 | |
when we open and look at the genomes of this bacteria. | 0:21:19 | 0:21:22 | |
We can do it now, we can sequence a whole genome of these bacteria | 0:21:22 | 0:21:24 | |
and see what are the exact changes that happen. | 0:21:24 | 0:21:27 | |
Typically, what genes changed and allowed them to mutate in such a way | 0:21:28 | 0:21:33 | |
it can grow in this higher drug concentration. | 0:21:33 | 0:21:37 | |
This is evolution in action. | 0:21:37 | 0:21:39 | |
Over millions of divisions, the bacteria's DNA changes. | 0:21:42 | 0:21:48 | |
Evolution happens here fairly fast, | 0:21:49 | 0:21:51 | |
in basically two weeks of experiment | 0:21:51 | 0:21:55 | |
we see a very dramatic increase in drug resistance, | 0:21:55 | 0:21:58 | |
1,000-fold increase in drug resistance. | 0:21:58 | 0:22:02 | |
So, yes, you might want to say evolution is happening | 0:22:02 | 0:22:05 | |
in front of our eyes, as we speak. | 0:22:05 | 0:22:09 | |
Used properly, antibiotics can kill bacteria and save lives, | 0:22:09 | 0:22:14 | |
but as these experiments show, | 0:22:16 | 0:22:19 | |
low levels of antibiotics encourage bacteria to develop resistance. | 0:22:19 | 0:22:24 | |
In the real world too, | 0:22:26 | 0:22:28 | |
our use of antibiotics may actually be causing more superbugs to emerge. | 0:22:28 | 0:22:33 | |
Superbugs were once rare and infrequent, | 0:22:41 | 0:22:44 | |
but they are now showing up across the world's major cities. | 0:22:44 | 0:22:47 | |
Professor Tim Walsh studies these newly emerging outbreaks, | 0:22:51 | 0:22:55 | |
and there's one region that concerns him most of all. | 0:22:55 | 0:23:00 | |
The southern Asian continent suffers from antibiotic resistance | 0:23:00 | 0:23:03 | |
far more than probably any other area on the planet. | 0:23:03 | 0:23:06 | |
For the last three years he's been travelling to Southern Asia | 0:23:08 | 0:23:11 | |
to understand why some of the poorest parts of the planet | 0:23:11 | 0:23:15 | |
are superbug hotspots. | 0:23:15 | 0:23:18 | |
He's on his way to Karachi's Civil Hospital, in Pakistan. | 0:23:26 | 0:23:30 | |
In both rich and poor countries, | 0:23:33 | 0:23:36 | |
resistant bacteria cause their most costly and deadly infections | 0:23:36 | 0:23:41 | |
in the places where people are most vulnerable - hospitals. | 0:23:41 | 0:23:46 | |
The doctors at the hospital are working with Prof Walsh | 0:23:48 | 0:23:51 | |
to identify and improve the conditions contributing to the spread of superbugs. | 0:23:51 | 0:23:57 | |
A lot of times you see them and they're not washing their hands. | 0:23:57 | 0:24:00 | |
This is one of the reasons we have so much infection. | 0:24:00 | 0:24:03 | |
I think the infection control issue here | 0:24:03 | 0:24:06 | |
clearly seems to be very important. | 0:24:06 | 0:24:08 | |
One of the key issues in places like the Civil Hospital | 0:24:08 | 0:24:12 | |
is sort of overcrowding of the wards and lack of infection control. | 0:24:12 | 0:24:16 | |
Windows are open so bacteria can kind of blow into | 0:24:17 | 0:24:20 | |
intensive care units etc, and there seems to be a lack of | 0:24:20 | 0:24:25 | |
understanding as to the importance of things like hand-washing | 0:24:25 | 0:24:29 | |
in moving from patient to patient, or indeed from ward to ward. | 0:24:29 | 0:24:33 | |
The doctors are facing dangerous infections, | 0:24:35 | 0:24:38 | |
in impossible conditions. | 0:24:38 | 0:24:40 | |
Professor Walsh has found | 0:24:40 | 0:24:42 | |
there are no dedicated infection control teams, | 0:24:42 | 0:24:44 | |
insufficient bacterial diagnosis, and no isolation rooms. | 0:24:44 | 0:24:49 | |
Well, the people in Karachi know about their limitations, | 0:24:52 | 0:24:56 | |
and that's the great thing, they're very open and honest about them, | 0:24:56 | 0:24:59 | |
they realise they must do something about it. | 0:24:59 | 0:25:02 | |
But there's another factor at play that the hospital can't control. | 0:25:03 | 0:25:07 | |
There is an easy availability | 0:25:07 | 0:25:09 | |
of the very thing needed to create superbugs. | 0:25:09 | 0:25:12 | |
In most parts of Asia, antibiotics can be purchased | 0:25:19 | 0:25:24 | |
freely from shops without prescription. | 0:25:24 | 0:25:27 | |
A problem that the doctors throughout the hospital | 0:25:27 | 0:25:30 | |
are aware of. | 0:25:30 | 0:25:32 | |
From the pharmacy right outside the hospital | 0:25:32 | 0:25:34 | |
I bought all these antibiotics and they cost me just 2.50 rupees. | 0:25:34 | 0:25:38 | |
Anyone can go and buy these. | 0:25:38 | 0:25:42 | |
Bought over the counter, antibiotics are misused and misunderstood, | 0:25:42 | 0:25:47 | |
taken even for things that they can't cure. | 0:25:47 | 0:25:50 | |
And there are no instructions, certainly not with these, on usage. | 0:25:52 | 0:25:55 | |
Yeah, they don't come with a leaflet. | 0:25:55 | 0:25:58 | |
And a lot of people just will go to the corner shop | 0:25:58 | 0:26:02 | |
and simply buy a whole range of antibiotics and simply self medicate | 0:26:02 | 0:26:06 | |
and you can see on this one here one tablet has obviously been sold | 0:26:06 | 0:26:10 | |
to one particular person - just to take one tablet is just crazy. | 0:26:10 | 0:26:14 | |
You're just exposing the bacteria to what we call | 0:26:14 | 0:26:17 | |
sub-killing-concentrations of that antibiotic. | 0:26:17 | 0:26:21 | |
And so you're actually not killing the bacteria, or indeed | 0:26:21 | 0:26:24 | |
preventing it from growing, and more or less all we're doing | 0:26:24 | 0:26:28 | |
to the bacteria is saying, | 0:26:28 | 0:26:29 | |
"OK, here's the antibiotic, become resistant." | 0:26:29 | 0:26:33 | |
It's not just the sale of antibiotics that's unregulated. | 0:26:35 | 0:26:38 | |
Elsewhere in Asia, outlets from the industrial-scale manufacture | 0:26:42 | 0:26:45 | |
of antibiotics have contaminated rivers and streams. | 0:26:45 | 0:26:50 | |
As a result, societies can be awash with antibiotics, | 0:26:54 | 0:26:59 | |
the perfect conditions for superbugs. | 0:26:59 | 0:27:02 | |
However, the conditions needed to create a superbug | 0:27:03 | 0:27:07 | |
are not just happening in Asia, but right across the world. | 0:27:07 | 0:27:11 | |
Professor Lance Price is a superbug tracker. | 0:27:16 | 0:27:19 | |
A few years ago, he was called to investigate a superbug | 0:27:21 | 0:27:25 | |
which helped to reveal how another use of antibiotics | 0:27:25 | 0:27:29 | |
was driving resistance. | 0:27:29 | 0:27:31 | |
Bacteria are everywhere. They're a natural part of our environment, | 0:27:33 | 0:27:38 | |
they're a natural part of us, in fact human beings are sort of | 0:27:38 | 0:27:43 | |
a walking ecosystem, we have bacteria that live in and on us, | 0:27:43 | 0:27:46 | |
one of the bacteria that I'm particularly interested in | 0:27:46 | 0:27:51 | |
is Staph aureus. | 0:27:51 | 0:27:53 | |
It's estimated the between 20% and 30% of humans | 0:27:53 | 0:27:57 | |
are colonised with Staph aureus, | 0:27:57 | 0:27:59 | |
and most of the time it doesn't pose a problem. | 0:27:59 | 0:28:02 | |
If Staph aureus does cause an infection, it is usually | 0:28:04 | 0:28:07 | |
straightforward to treat with an antibiotic called methicillin. | 0:28:07 | 0:28:11 | |
But when it develops resistance to methicillin | 0:28:14 | 0:28:18 | |
it becomes a superbug we've all heard of, MRSA. | 0:28:18 | 0:28:21 | |
This is a picture of methicillin-resistant Staph aureus. | 0:28:23 | 0:28:26 | |
Methicillin-resistant Staph aureus and regular Staph aureus | 0:28:26 | 0:28:29 | |
don't look any different in a photo like this, | 0:28:29 | 0:28:31 | |
but when you look at the DNA, you'll see very distinct differences. | 0:28:31 | 0:28:35 | |
MRSA carries genes that make it resistant to methicillin, | 0:28:35 | 0:28:39 | |
that's why we call it methicillin-resistant Staph aureus, or MRSA. | 0:28:39 | 0:28:43 | |
He uses these genetic differences as clues | 0:28:44 | 0:28:47 | |
to lead him to the source of the outbreaks. | 0:28:47 | 0:28:49 | |
We crack these cells open and we sequence the DNA, | 0:28:49 | 0:28:53 | |
and then we use that to trace the evolutionary history of these bugs | 0:28:53 | 0:28:57 | |
and determine how and sometimes when | 0:28:57 | 0:29:00 | |
they became resistant to methicillin. | 0:29:00 | 0:29:02 | |
Three years ago, he discovered a new strain of MRSA | 0:29:06 | 0:29:11 | |
in 18 different countries, including the USA and in Europe. | 0:29:11 | 0:29:15 | |
And there was one thing that seemed to connect them all. | 0:29:16 | 0:29:20 | |
A new strain of MRSA emerged that we'd never seen before, | 0:29:20 | 0:29:24 | |
and when we started tracking it back we found out that | 0:29:24 | 0:29:27 | |
most of the people who were getting it were actually employed in the | 0:29:27 | 0:29:31 | |
livestock industry, so people that had direct exposure to food animals. | 0:29:31 | 0:29:35 | |
And that set off an investigation for us. | 0:29:35 | 0:29:39 | |
The genetic trail revealed this strain of MRSA | 0:29:39 | 0:29:42 | |
had passed into these people from pigs. | 0:29:42 | 0:29:46 | |
But then they went further. | 0:29:47 | 0:29:50 | |
They tried to follow the genes back to a time before | 0:29:50 | 0:29:54 | |
the MRSA became resistant. | 0:29:54 | 0:29:56 | |
And what we found was a big surprise to us, | 0:29:56 | 0:29:59 | |
we found that in fact that this new strain had started off in people | 0:29:59 | 0:30:04 | |
but it was not MRSA, it was just Staph aureus, or SA, | 0:30:04 | 0:30:08 | |
it spread to pigs, and that's where it became resistant to methicillin. | 0:30:08 | 0:30:14 | |
Professor Price had discovered that this ordinary Staph aureus bacteria | 0:30:17 | 0:30:21 | |
had mutated while it was in the livestock, | 0:30:21 | 0:30:25 | |
to become potentially deadly. | 0:30:25 | 0:30:27 | |
To him, the reason was obvious, antibiotics. | 0:30:30 | 0:30:34 | |
The simplest explanation is that we're using | 0:30:35 | 0:30:38 | |
lots and lots of antibiotics in food animal production. | 0:30:38 | 0:30:41 | |
Most of the time they're just being added to animal feed, | 0:30:41 | 0:30:44 | |
so they're being mixed in giant silos of feed | 0:30:44 | 0:30:48 | |
and given on a routine basis, just basically with every meal | 0:30:48 | 0:30:53 | |
that animals are getting a little bit of antibiotics. | 0:30:53 | 0:30:56 | |
Many farmers thought it was the best way | 0:30:56 | 0:30:58 | |
to keep closely packed animals healthy | 0:30:58 | 0:31:01 | |
and for them to grow faster, | 0:31:01 | 0:31:04 | |
but Professor Price believes the superbug he was tracking | 0:31:04 | 0:31:07 | |
was created as a result of this kind of antibiotic use. | 0:31:07 | 0:31:11 | |
We're raising animals under the conditions that we know | 0:31:11 | 0:31:14 | |
lead to the spread of bacteria between people, | 0:31:14 | 0:31:17 | |
and then we add the magic ingredient which is antibiotics, | 0:31:17 | 0:31:20 | |
which just virtually guarantees that we're going to have | 0:31:20 | 0:31:22 | |
drug-resistant bacteria. | 0:31:22 | 0:31:23 | |
In 2006, the European Union banned the use of antibiotics | 0:31:23 | 0:31:29 | |
as growth promoters in animal feed. | 0:31:29 | 0:31:32 | |
But elsewhere in the world, it is still being used in vast quantities. | 0:31:32 | 0:31:37 | |
In the United States we use 29 million pounds of antibiotics | 0:31:37 | 0:31:41 | |
every year in food animal production. | 0:31:41 | 0:31:43 | |
I mean, you know, these are the crown jewels of modern medicine, | 0:31:43 | 0:31:47 | |
they're being used like cheap production tools. | 0:31:47 | 0:31:49 | |
There is a movement in the US to change this practice. | 0:31:52 | 0:31:57 | |
Professor Price is working with farmers who are trying new ways | 0:31:57 | 0:32:00 | |
of keeping animals healthy, | 0:32:00 | 0:32:01 | |
without constant use of antibiotics in the feed. | 0:32:01 | 0:32:05 | |
-Like to come in and see what we're doing here? -I would. | 0:32:05 | 0:32:09 | |
Yeah. Give you some coveralls and some booties for you. | 0:32:09 | 0:32:13 | |
Removing antibiotics from the feed means farmers need to take | 0:32:14 | 0:32:18 | |
other measures to avoid their livestock getting infections. | 0:32:18 | 0:32:22 | |
I have to wear these in a lab sometimes. | 0:32:22 | 0:32:25 | |
In that case, we're protecting ourselves from the microbes | 0:32:25 | 0:32:28 | |
rather than the turkeys from us. | 0:32:28 | 0:32:31 | |
But working this way means farms are less likely | 0:32:31 | 0:32:34 | |
to encourage superbugs to emerge. | 0:32:34 | 0:32:38 | |
Everybody would say, | 0:32:38 | 0:32:39 | |
"There's no way you're going to be able to grow turkeys without antibiotics." | 0:32:39 | 0:32:43 | |
So we started trials and learned from that, | 0:32:43 | 0:32:45 | |
that we needed to give the birds more space | 0:32:45 | 0:32:48 | |
and really go out of your way to have the best animal husbandry, | 0:32:48 | 0:32:52 | |
that they don't get stressed. | 0:32:52 | 0:32:54 | |
And now, if we do get a sick flock, which is rare, | 0:32:54 | 0:32:58 | |
but if we get one and we have to treat it, | 0:32:58 | 0:33:00 | |
we can use the simplest antibiotic like a tetracycline, | 0:33:00 | 0:33:03 | |
and it usually works great. | 0:33:03 | 0:33:05 | |
For where it continues, large-scale use of antibiotics in animal feed | 0:33:08 | 0:33:14 | |
can create the right environment for superbug emergence. | 0:33:14 | 0:33:17 | |
Bacteria don't wear lapel pins. | 0:33:20 | 0:33:22 | |
They're not confined to any geographic area, | 0:33:22 | 0:33:24 | |
and so what we do here in the United States can potentially impact you. | 0:33:24 | 0:33:29 | |
So as we create these multi-drug-resistant pathogens, | 0:33:29 | 0:33:33 | |
those pathogens can then spread around the world. | 0:33:33 | 0:33:36 | |
And so you should just be as concerned as I am | 0:33:36 | 0:33:39 | |
about what we're doing over here. | 0:33:39 | 0:33:40 | |
Wherever a superbug outbreak occurs in the world, | 0:33:47 | 0:33:51 | |
doctors across the globe start to worry, | 0:33:51 | 0:33:55 | |
because regardless of where they first emerge, | 0:33:55 | 0:33:57 | |
a superbug can soon become a citizen of the world. | 0:33:57 | 0:34:01 | |
We carry about 100 trillion bacteria in us, | 0:34:02 | 0:34:06 | |
therefore, when we travel the world, they travel the world. | 0:34:06 | 0:34:09 | |
Any types of resistance that occurs in one country | 0:34:09 | 0:34:12 | |
can very easily be transported around the world, almost in real time. | 0:34:12 | 0:34:16 | |
With the rising levels of air travel, | 0:34:19 | 0:34:22 | |
resistant bacteria have hitched rides across the globe. | 0:34:22 | 0:34:25 | |
Probably in about the last 15 to 20 years, | 0:34:25 | 0:34:28 | |
we've managed to contaminate the whole of the planet. | 0:34:28 | 0:34:31 | |
If you go to the north of Norway, or even down into Australia, | 0:34:31 | 0:34:34 | |
down to Tasmania, you will find these type of resistances. | 0:34:34 | 0:34:37 | |
Not only are superbugs being found all over the world, | 0:34:38 | 0:34:42 | |
scientists are finding that these bacteria | 0:34:42 | 0:34:45 | |
are becoming harder and harder to treat. | 0:34:45 | 0:34:47 | |
It's this problem that Professor Tim Walsh grapples with every day. | 0:34:51 | 0:34:56 | |
This a very quick illustration of how resistance has evolved | 0:34:56 | 0:35:00 | |
over about the last 20 years. | 0:35:00 | 0:35:02 | |
Each white disc on these plates contains a different antibiotic. | 0:35:04 | 0:35:08 | |
A clear circle indicates the antibiotic is working | 0:35:10 | 0:35:14 | |
and killing the bacteria. | 0:35:14 | 0:35:16 | |
This E. coli from India about 20 years ago | 0:35:18 | 0:35:21 | |
is fully sensitive to the series of antibiotics | 0:35:21 | 0:35:24 | |
which we would use to treat E. coli infections. | 0:35:24 | 0:35:28 | |
12 years ago, the E. coli had started to become resistant | 0:35:30 | 0:35:33 | |
to some of the antibiotics, | 0:35:33 | 0:35:36 | |
but the newest strain has shown unprecedented levels of resistance. | 0:35:36 | 0:35:41 | |
You can see here it's virtually totally resistant. | 0:35:42 | 0:35:45 | |
The only antibiotic that shows any activity | 0:35:45 | 0:35:48 | |
against this particular organism, is this antibiotic here, | 0:35:48 | 0:35:51 | |
which has some issues with toxicity, | 0:35:51 | 0:35:53 | |
and it's at the moment about 40, 50 years old. | 0:35:53 | 0:35:57 | |
We're starting to have a bit of a renaissance with it, | 0:35:57 | 0:35:59 | |
because clearly you can see that we have nothing left. | 0:35:59 | 0:36:02 | |
We are beginning to see this level of resistance appear | 0:36:02 | 0:36:06 | |
all over the world. | 0:36:06 | 0:36:08 | |
Bacteria that only respond to a few rarely used antibiotics. | 0:36:09 | 0:36:14 | |
And the trouble is, | 0:36:15 | 0:36:17 | |
these antibiotics of last resort can often be toxic themselves. | 0:36:17 | 0:36:22 | |
Scientists believe there is an urgent need | 0:36:24 | 0:36:27 | |
to re-stock our arsenal with new antibiotics. | 0:36:27 | 0:36:30 | |
It's a hunt that has taken Professor Hazel Barton across the globe. | 0:36:49 | 0:36:55 | |
I get to travel the world, I get to see amazing things, | 0:37:00 | 0:37:04 | |
so I just love it! | 0:37:04 | 0:37:05 | |
You might think that new antibiotics were created in a lab, | 0:37:07 | 0:37:10 | |
or discovered deep in the rainforest, | 0:37:10 | 0:37:14 | |
but actually most of them have been found in the dirt. | 0:37:14 | 0:37:18 | |
Almost all of the antibiotics that we use now | 0:37:19 | 0:37:23 | |
have come from soil micro-organisms. | 0:37:23 | 0:37:25 | |
The procedures that we have in the lab for finding antibiotics | 0:37:25 | 0:37:29 | |
is literally to pull the microbes out of this dirt and grow them. | 0:37:29 | 0:37:33 | |
More than three-quarters of the antibiotics we regularly use | 0:37:34 | 0:37:38 | |
in hospitals today were taken from microbes in the soil. | 0:37:38 | 0:37:41 | |
And the trouble is, we've been doing that for 50 years | 0:37:45 | 0:37:47 | |
and we keep finding the same things. | 0:37:47 | 0:37:49 | |
And the best microbes for producing antibiotics are bacteria themselves. | 0:37:51 | 0:37:56 | |
To find new antibiotics, Professor Barton has to hunt down new bacteria | 0:37:58 | 0:38:03 | |
in some of the most untouched places on Earth. | 0:38:03 | 0:38:07 | |
Hundreds of metres underground. | 0:38:08 | 0:38:11 | |
Oh, it's slippery here. | 0:38:30 | 0:38:32 | |
For bacteria, | 0:38:34 | 0:38:35 | |
these caves are one of the toughest places in the world to survive. | 0:38:35 | 0:38:39 | |
Between where we're standing right now and the surface, | 0:38:42 | 0:38:45 | |
there's about 1,000 feet of rock. | 0:38:45 | 0:38:47 | |
So for anything that's happening on the surface, | 0:38:49 | 0:38:52 | |
all that energy from plants and animals, for that to come here, | 0:38:52 | 0:38:56 | |
it has to get through all that rock, and it can't do that very easily. | 0:38:56 | 0:39:01 | |
So we end up with a very starved environment, | 0:39:02 | 0:39:05 | |
where there's hardly any energy available. | 0:39:05 | 0:39:09 | |
These caves may look peaceful and still, | 0:39:09 | 0:39:12 | |
but they are, in fact, a battlefield. | 0:39:12 | 0:39:16 | |
With so few resources available, | 0:39:16 | 0:39:19 | |
bacteria must fight each other to survive. | 0:39:19 | 0:39:22 | |
They become either much more careful of their resources | 0:39:26 | 0:39:31 | |
in defending them, | 0:39:31 | 0:39:32 | |
or they get a lot more aggressive in stealing someone else's resources. | 0:39:32 | 0:39:37 | |
They do this by producing an arsenal of chemical weapons. | 0:39:38 | 0:39:42 | |
Professor Barton has been collecting these weapons | 0:39:44 | 0:39:47 | |
in the hope they might be used as antibiotics. | 0:39:47 | 0:39:51 | |
Last year, she captured one type of bacteria | 0:39:52 | 0:39:55 | |
that produced over 38 different bacteria-killing chemicals. | 0:39:55 | 0:40:01 | |
To put that in perspective, | 0:40:01 | 0:40:03 | |
there's only about 40 antimicrobial drugs in the clinic right now. | 0:40:03 | 0:40:08 | |
So one bug from this cave was able to make | 0:40:08 | 0:40:11 | |
almost as many as we have available to us in the clinic. | 0:40:11 | 0:40:15 | |
Not all of those are going to be useful as medicines, | 0:40:15 | 0:40:18 | |
but the potential becomes huge. | 0:40:18 | 0:40:20 | |
I mean, we've pulled out 4,000 microbes, | 0:40:20 | 0:40:24 | |
so it's almost like a chemical universe | 0:40:24 | 0:40:26 | |
and we are kind of playing on the edges of it | 0:40:26 | 0:40:30 | |
with antimicrobial compounds and there's this huge vast | 0:40:30 | 0:40:33 | |
unknown space that we've yet to kind of explore to see what's out there. | 0:40:33 | 0:40:38 | |
The work of scientists like Professor Barton | 0:40:40 | 0:40:43 | |
is becoming increasingly important, as any new antibiotic discovery | 0:40:43 | 0:40:47 | |
will enable us to retain our hold over the superbugs. | 0:40:47 | 0:40:52 | |
But eventually, bacteria will always find a way to become resistant | 0:40:53 | 0:40:58 | |
to even the new antibiotics. | 0:40:58 | 0:41:01 | |
If we are going to finally overcome the problem of resistance | 0:41:04 | 0:41:07 | |
we are going to need a whole new approach. | 0:41:07 | 0:41:10 | |
On the face of it, this seems an unlikely place to discover | 0:41:29 | 0:41:32 | |
a new strategy for fighting superbugs. | 0:41:32 | 0:41:36 | |
It's a sewage works in Buckinghamshire. | 0:41:36 | 0:41:41 | |
But microbiologist Dr David Harper believes the answer | 0:41:41 | 0:41:45 | |
may be found here. | 0:41:45 | 0:41:48 | |
He's hoping to exploit the weapons technology of a creature | 0:41:48 | 0:41:52 | |
that has developed its own way to fight bacteria. | 0:41:52 | 0:41:55 | |
Bacteria have been on the Earth for billions of years. | 0:41:57 | 0:42:01 | |
That's why they're so tricky. | 0:42:01 | 0:42:03 | |
But there's something else that's been on the Earth | 0:42:03 | 0:42:05 | |
for billions of years. | 0:42:05 | 0:42:06 | |
And it knows how to deal with bacteria. | 0:42:06 | 0:42:09 | |
That's what I'm here to collect. | 0:42:09 | 0:42:10 | |
-Good to see you. -And you, David. -Let's go and get some good ones. | 0:42:10 | 0:42:15 | |
Raw sewage is the perfect breeding ground for bacteria. | 0:42:16 | 0:42:20 | |
But that also makes it the ideal home | 0:42:22 | 0:42:24 | |
for the ultimate bacterial predator. | 0:42:24 | 0:42:26 | |
He wants to enlist that predator to fight for us in the superbug war. | 0:42:28 | 0:42:33 | |
In there, although we can't see it, there's a war going on. | 0:42:33 | 0:42:37 | |
There are billions of bacteria struggling for existence, | 0:42:37 | 0:42:41 | |
and tens of billions of bacteriophages. | 0:42:41 | 0:42:44 | |
Viruses that only and specifically affect and kill bacteria. | 0:42:44 | 0:42:49 | |
And they are fighting in there, as we speak. | 0:42:49 | 0:42:53 | |
Just like humans, bacteria can be infected and killed by viruses. | 0:42:54 | 0:42:59 | |
Bacteriophages are the most common and diverse predators on Earth. | 0:42:59 | 0:43:04 | |
There are 10,000 billion, billion, billion, | 0:43:06 | 0:43:10 | |
bacteriophages on the planet. | 0:43:10 | 0:43:12 | |
We haven't actually counted, that is an estimate. | 0:43:12 | 0:43:14 | |
Dr Harper wants to get these bacterial viruses | 0:43:16 | 0:43:19 | |
fighting on our side in the superbug war. | 0:43:19 | 0:43:23 | |
"Bacteriophage" literally means "bacteria eater". | 0:43:23 | 0:43:29 | |
They work by landing on the bacteria, | 0:43:29 | 0:43:32 | |
injecting in their own DNA, | 0:43:32 | 0:43:35 | |
then reproducing themselves inside the bacteria until it bursts. | 0:43:35 | 0:43:39 | |
Back in his company's lab, | 0:43:42 | 0:43:45 | |
Dr Harper is attempting to harness the power | 0:43:45 | 0:43:47 | |
of these bacterial predators. | 0:43:47 | 0:43:50 | |
It's a tricky business. | 0:43:50 | 0:43:53 | |
To kill disease-causing bacteria, | 0:43:53 | 0:43:55 | |
you need the particular phage which attacks that bacteria species. | 0:43:55 | 0:44:00 | |
We go and collect the sewage, we bring it back here, | 0:44:00 | 0:44:05 | |
we put the sewage into a culture of the target bacterial species. | 0:44:05 | 0:44:12 | |
There are lots of different phages in there, | 0:44:12 | 0:44:14 | |
I said there were billions - there are. Maybe thousands, | 0:44:14 | 0:44:17 | |
maybe hundreds, will hit that particular species. | 0:44:17 | 0:44:20 | |
In a few cases, you might have a species where only a few will hit it, | 0:44:20 | 0:44:25 | |
but still, if they're there, they will bind, | 0:44:25 | 0:44:29 | |
they will kill, they will multiply | 0:44:29 | 0:44:32 | |
and you can pick them and grow them. | 0:44:32 | 0:44:34 | |
Using viruses to kill bacteria | 0:44:40 | 0:44:42 | |
sounds like an attractive idea in principle, | 0:44:42 | 0:44:44 | |
but in practice, working with live organisms has proven difficult. | 0:44:44 | 0:44:50 | |
But Dr Harper is drawn to this field of research | 0:44:52 | 0:44:56 | |
because phages offer one significant advantage over antibiotics. | 0:44:56 | 0:45:00 | |
Antibiotics can't change. | 0:45:03 | 0:45:06 | |
If the bacteria generate resistance, that's it, | 0:45:06 | 0:45:08 | |
you need a new antibiotic. | 0:45:08 | 0:45:09 | |
With phages, the bacteria are their lunch. | 0:45:09 | 0:45:12 | |
If they can't multiply, they die out. If they can, they grow. | 0:45:12 | 0:45:17 | |
So when the bacteria change, a few phages will be in there, | 0:45:17 | 0:45:21 | |
which can grow in the new ones. | 0:45:21 | 0:45:23 | |
That mutation is then preferred, those phages will multiply | 0:45:23 | 0:45:28 | |
and come to dominate. | 0:45:28 | 0:45:30 | |
The bacteria will change again, a few of those will be able to grow, | 0:45:30 | 0:45:34 | |
they grow again, they amplify, they come to dominate. | 0:45:34 | 0:45:37 | |
It's an arms race. | 0:45:37 | 0:45:38 | |
Tapping into this arms race would hand us a key advantage | 0:45:41 | 0:45:45 | |
because the bacteriophages are able to evolve. | 0:45:45 | 0:45:49 | |
If we are able to enlist them to fight for us, | 0:45:50 | 0:45:53 | |
they will keep fighting for us, even as the bacteria change. | 0:45:53 | 0:45:58 | |
They are in many ways a perfect drug, in many ways they aren't. | 0:45:58 | 0:46:03 | |
One of the most telling things against bacteriophages as drugs | 0:46:03 | 0:46:07 | |
is that nobody has yet developed one. | 0:46:07 | 0:46:10 | |
Dr Harper's company have seen some early successes | 0:46:14 | 0:46:18 | |
and are now planning a trial to treat lung infections | 0:46:18 | 0:46:21 | |
often affecting cystic fibrosis sufferers. | 0:46:21 | 0:46:25 | |
We hope that the results in cystic fibrosis will be convincing. | 0:46:27 | 0:46:32 | |
We hope to move on to the large clinical trials | 0:46:32 | 0:46:35 | |
of hundreds of patients, which will underpin | 0:46:35 | 0:46:38 | |
progressing this to market to improve people's lives, to save people's lives. | 0:46:38 | 0:46:43 | |
There's a long way still to go, but we're working on it. | 0:46:43 | 0:46:46 | |
Right now, phage medicines are still in the very early stages | 0:46:49 | 0:46:54 | |
but new developments in understanding exactly how | 0:46:58 | 0:47:01 | |
bacteria become deadly are giving hope that there could be | 0:47:01 | 0:47:05 | |
another way to outsmart them. | 0:47:05 | 0:47:06 | |
Princeton University in New Jersey. | 0:47:10 | 0:47:13 | |
Here, a team are taking a radically new approach, | 0:47:16 | 0:47:19 | |
one that has led to an unexpected breakthrough | 0:47:21 | 0:47:24 | |
in the fight against deadly bacteria. | 0:47:24 | 0:47:27 | |
Professor Bonnie Bassler has spent her career | 0:47:31 | 0:47:34 | |
getting in to their world. | 0:47:34 | 0:47:37 | |
I love bacteria. I think most of the things | 0:47:41 | 0:47:44 | |
they do on this earth are fantastic and essential, | 0:47:44 | 0:47:47 | |
but bacteria have features, bells and whistles, different processes, | 0:47:47 | 0:47:52 | |
that they are, that they have for fighting in their own environments. | 0:47:52 | 0:47:56 | |
And when those get unleashed in a human or in an animal | 0:47:56 | 0:48:00 | |
or in a plant, it can kill us. | 0:48:00 | 0:48:02 | |
With antibiotics, we have been attacking bacteria, | 0:48:03 | 0:48:07 | |
forcing them to evolve resistance. | 0:48:07 | 0:48:09 | |
But Professor Bassler thinks that we may not have to be so aggressive. | 0:48:11 | 0:48:15 | |
Instead of just smashing them to smithereens | 0:48:15 | 0:48:18 | |
like we've done with traditional antibiotics, if we could learn enough | 0:48:18 | 0:48:21 | |
of their secrets, and get them to spill their guts a little bit | 0:48:21 | 0:48:26 | |
and tell us how they work, we could just get them to behave. | 0:48:26 | 0:48:31 | |
And do behaviour modification instead of killing them. | 0:48:31 | 0:48:35 | |
Compared to us, bacteria are so incredibly small | 0:48:36 | 0:48:41 | |
that on their own, they shouldn't be able to hurt us at all. | 0:48:41 | 0:48:44 | |
If one or a few bacteria release | 0:48:46 | 0:48:49 | |
their mostly deadly arsenal of toxins, they have no effect. | 0:48:49 | 0:48:53 | |
I mean, this is not a David and Goliath, this is like | 0:48:53 | 0:48:56 | |
way beyond that, so the question is, | 0:48:56 | 0:48:58 | |
how can these bacteria have us on our knees, | 0:48:58 | 0:49:01 | |
right, how can it be that they can actually kill us? | 0:49:01 | 0:49:05 | |
Bacteria don't attempt to attack us on their own, | 0:49:07 | 0:49:10 | |
they wait until there are enough of them and then act all at once. | 0:49:10 | 0:49:15 | |
You can think of the bacteria, each individual bacterium as a soldier, | 0:49:15 | 0:49:20 | |
and so you have these masses of soldiers, but it's only useful | 0:49:20 | 0:49:24 | |
when somebody says "charge", right, so the question is | 0:49:24 | 0:49:29 | |
what's the information that tells the bacteria now is the time to attack? | 0:49:29 | 0:49:35 | |
If we could find a way to stop the bacteria attacking together, | 0:49:37 | 0:49:41 | |
they wouldn't be able to harm us. | 0:49:41 | 0:49:43 | |
But understanding how they co-ordinate their attack | 0:49:45 | 0:49:50 | |
is incredibly difficult | 0:49:50 | 0:49:52 | |
because bacteria are hidden from sight. | 0:49:52 | 0:49:55 | |
But there is a type of bacteria that you can see, | 0:49:55 | 0:49:59 | |
and they have a rather unusual relationship. | 0:49:59 | 0:50:03 | |
The Hawaiian bob-tailed squid is a master of disguise. | 0:50:11 | 0:50:15 | |
In the day, it disappears into the sea bed, | 0:50:15 | 0:50:21 | |
but when it comes out to feed at night, it's even more ingenious. | 0:50:21 | 0:50:26 | |
At night, this is like the stealth bomber of the ocean, | 0:50:29 | 0:50:31 | |
it likes to cloak itself in an invisible device. | 0:50:31 | 0:50:34 | |
If it were to just swim around, | 0:50:34 | 0:50:35 | |
the starlight or moonlight would hit its back | 0:50:35 | 0:50:38 | |
and it would cast a shadow on the sea floor here | 0:50:38 | 0:50:42 | |
and then predators that could see that shadow | 0:50:42 | 0:50:44 | |
could calculate its trajectory, and eat it. | 0:50:44 | 0:50:46 | |
To eliminate their shadow, | 0:50:48 | 0:50:50 | |
these squid project light down onto the sea floor. | 0:50:50 | 0:50:55 | |
So by matching how much starlight or moonlight hits its back | 0:50:55 | 0:50:59 | |
with how much light comes out of its body, there's no shadow. | 0:50:59 | 0:51:03 | |
So it's a fantastic sleight of hand, sleight of tentacle, | 0:51:03 | 0:51:08 | |
if you will, it's a fantastic anti-predation device | 0:51:08 | 0:51:12 | |
because it makes it invisible at night. | 0:51:12 | 0:51:15 | |
And this incredible invisibility cloak is created by bacteria. | 0:51:16 | 0:51:22 | |
There's a bacterium that lives in the body of the squid, | 0:51:22 | 0:51:26 | |
the bacterium's name is Vibrio ficheri, and it makes light, | 0:51:26 | 0:51:31 | |
so the squid gives the bacterium a home, | 0:51:31 | 0:51:33 | |
the bacterium gives the squid light, | 0:51:33 | 0:51:36 | |
and the squid uses the light to protect itself from predators. | 0:51:36 | 0:51:39 | |
But just as a single dangerous bacteria would not be enough | 0:51:46 | 0:51:50 | |
to make us sick, a single glowing bacteria would never produce | 0:51:50 | 0:51:55 | |
enough light to help the squid. | 0:51:55 | 0:51:58 | |
For the bacteria to be useful, there must be lots of them. | 0:51:58 | 0:52:01 | |
So the bacteria wait until there are enough of them, | 0:52:02 | 0:52:06 | |
and only then, all start glowing at exactly the same time. | 0:52:06 | 0:52:11 | |
When this was initially discovered, | 0:52:11 | 0:52:13 | |
the idea that bacteria could do something as a group was revelatory. | 0:52:13 | 0:52:18 | |
The bacteria were working together, | 0:52:21 | 0:52:23 | |
but the question was, how were they doing it? | 0:52:23 | 0:52:27 | |
The beauty of these marine bacteria is that they glow in the dark, | 0:52:28 | 0:52:33 | |
so they could experiment to see what exactly caused them | 0:52:33 | 0:52:38 | |
to start making light. | 0:52:38 | 0:52:39 | |
They discovered the bacteria were producing a chemical messenger - | 0:52:42 | 0:52:47 | |
they were talking to each other. | 0:52:47 | 0:52:50 | |
As they grow and divide, | 0:52:50 | 0:52:52 | |
they all make and release these molecules. | 0:52:52 | 0:52:55 | |
When there's more cells, the molecule outside the cells | 0:52:55 | 0:52:59 | |
increases in proportion to cell number. | 0:52:59 | 0:53:01 | |
And when the molecule hits a certain amount, | 0:53:01 | 0:53:04 | |
the bacteria have receptors on their surfaces, they detect that the | 0:53:04 | 0:53:07 | |
molecule is there and then they all change their behaviour in unison. | 0:53:07 | 0:53:11 | |
Using these molecules, the bacteria were able to detect | 0:53:15 | 0:53:19 | |
when other bacteria were around them. | 0:53:19 | 0:53:22 | |
And by communicating with each other, the bacteria were able to | 0:53:23 | 0:53:26 | |
achieve something they could never achieve as individuals. | 0:53:26 | 0:53:31 | |
This behaviour is called quorum sensing. | 0:53:31 | 0:53:34 | |
Sometimes, the way I think of it, is if you want to move a piano | 0:53:34 | 0:53:38 | |
from over there, to over there, you don't try to do that yourself, | 0:53:38 | 0:53:42 | |
you get all your friends, everybody grabs and you say, | 0:53:42 | 0:53:44 | |
"One, two, three, lift." | 0:53:44 | 0:53:46 | |
And then you can carry out this task as a co-ordinated synchronous group | 0:53:46 | 0:53:51 | |
that you couldn't do, if you were just acting on your own. | 0:53:51 | 0:53:55 | |
Once they'd discovered the glowing bacteria could talk to each other | 0:54:02 | 0:54:07 | |
using chemicals, Professor Bassler began to wonder if this was the way | 0:54:07 | 0:54:10 | |
dangerous bacteria were coordinating their attack. | 0:54:10 | 0:54:15 | |
And so I thought, "Well, I wonder if anybody else makes this molecule." | 0:54:17 | 0:54:21 | |
So I just collected every bacterium I could get my hands on. | 0:54:21 | 0:54:25 | |
And every bacterium I tried that with, it worked. | 0:54:33 | 0:54:37 | |
And there was this moment, I still get goose pimples with that, | 0:54:37 | 0:54:40 | |
there's this moment where I thought, | 0:54:40 | 0:54:42 | |
"Holy cow, they're talking between species, | 0:54:42 | 0:54:45 | |
"they all make this molecule." | 0:54:45 | 0:54:47 | |
It looked like all bacteria could communicate using these molecules. | 0:54:50 | 0:54:56 | |
This had incredible implications. | 0:54:56 | 0:54:59 | |
If she could interrupt these conversations, | 0:54:59 | 0:55:01 | |
she could get the bacteria to stop their group behaviour. | 0:55:01 | 0:55:05 | |
We know what these molecules are, at least some of them, | 0:55:05 | 0:55:07 | |
these quorum-sensing molecules, so we've made antagonists, right, | 0:55:07 | 0:55:11 | |
molecules that look kind of like the real things, | 0:55:11 | 0:55:13 | |
but they jam the receptors. | 0:55:13 | 0:55:15 | |
And so if you add those, it's like static, you know, | 0:55:15 | 0:55:18 | |
you add these anti-quorum-sensing molecules, the bacteria can't hear. | 0:55:18 | 0:55:21 | |
Professor Bassler had found a way | 0:55:25 | 0:55:27 | |
to stop the glow-in-the-dark bacteria from talking. | 0:55:27 | 0:55:31 | |
Could she do the same with dangerous bacteria | 0:55:31 | 0:55:34 | |
and prevent them from launching their attacks? | 0:55:34 | 0:55:37 | |
We started this work with Vibrio haveri and Vibrio ficheri, | 0:55:38 | 0:55:42 | |
these beautiful bio-luminescent bacteria, | 0:55:42 | 0:55:45 | |
but they have a nasty cousin, Vibrio cholera. | 0:55:45 | 0:55:49 | |
Those two bacteria make this beautiful light, this guy kills you. | 0:55:49 | 0:55:53 | |
Although completely eradicated in the UK, | 0:55:55 | 0:55:58 | |
the cholera bacteria is responsible for over 100,000 deaths | 0:55:58 | 0:56:02 | |
in the developing world every year. | 0:56:02 | 0:56:05 | |
So we transferred what we learned | 0:56:05 | 0:56:07 | |
from the glow-in-the-dark bacterium to this bacterium. | 0:56:07 | 0:56:11 | |
Professor Bassler can measure the level of a protein | 0:56:11 | 0:56:16 | |
that cholera bacteria produce that makes them deadly. | 0:56:16 | 0:56:19 | |
This is the protein that cholera makes | 0:56:19 | 0:56:21 | |
that lets it adhere to your intestine. | 0:56:21 | 0:56:23 | |
It has to make this. It's step one in the infection | 0:56:23 | 0:56:26 | |
and that makes it virulent. | 0:56:26 | 0:56:28 | |
So then what we did was, we added our anti-quorum-sensing molecule | 0:56:28 | 0:56:31 | |
at different amounts to cholera cells, | 0:56:31 | 0:56:34 | |
and if we add more and more and more of our molecule, | 0:56:34 | 0:56:36 | |
what you can see is, | 0:56:36 | 0:56:37 | |
it makes cholera incapable of making that virulence protein, | 0:56:37 | 0:56:42 | |
and incapable of making an infection. | 0:56:42 | 0:56:44 | |
This is just the beginning for Professor Bassler and her team, | 0:56:48 | 0:56:52 | |
as other researchers around the world are now investigating | 0:56:52 | 0:56:56 | |
whether this method of silencing the bacteria | 0:56:56 | 0:56:58 | |
has the potential to work where antibiotics are failing. | 0:56:58 | 0:57:02 | |
Scientists have entered a new stage in the battle with superbugs. | 0:57:19 | 0:57:24 | |
It may be that we have underestimated our enemy. | 0:57:27 | 0:57:30 | |
They're probably smarter than I am. | 0:57:32 | 0:57:34 | |
They're able to adjust fire much quicker than I can | 0:57:34 | 0:57:36 | |
so they're able to develop resistance a whole lot faster | 0:57:36 | 0:57:39 | |
than I can develop an antibiotic. | 0:57:39 | 0:57:40 | |
But around the world, scientists are taking up | 0:57:46 | 0:57:49 | |
this cat and mouse challenge. | 0:57:49 | 0:57:51 | |
It is a game. They're playing their game and we need to play our game. | 0:57:53 | 0:57:58 | |
We each need to do our best move. | 0:57:58 | 0:58:01 | |
We are understanding bacteria better than ever before | 0:58:05 | 0:58:08 | |
but maybe we don't have to triumph over all, | 0:58:10 | 0:58:14 | |
we just have to stay one step ahead. | 0:58:14 | 0:58:18 | |
We don't have to totally win, that's not the goal. | 0:58:18 | 0:58:21 | |
The goal is simply to find out enough to be able to do something useful | 0:58:21 | 0:58:26 | |
and then let the next scientist find out the next thing that's enough | 0:58:26 | 0:58:29 | |
to do something useful. | 0:58:29 | 0:58:31 | |
Subtitles by Red Bee Media Ltd | 0:58:43 | 0:58:46 |