0:00:03 > 0:00:06All around us there is an invisible world.
0:00:12 > 0:00:16The microscopic world of bacteria.
0:00:19 > 0:00:21Some of these bacteria are going rogue,
0:00:21 > 0:00:26becoming superbugs that we can't control.
0:00:29 > 0:00:31They're probably smarter than I am.
0:00:31 > 0:00:33They're able to adjust fire much quicker than me
0:00:33 > 0:00:36so they're able to develop resistance a whole lot faster
0:00:36 > 0:00:37than I can develop an antibiotic.
0:00:41 > 0:00:44Antibiotics are one of the miracles of modern medicine
0:00:46 > 0:00:49and scientists now worry that superbugs are emerging
0:00:49 > 0:00:53which are becoming totally resistant to these drugs.
0:00:53 > 0:00:58That's the scary day, that's the day when for some unlucky person
0:00:58 > 0:01:03their day has come, right, that the drugs no longer work.
0:01:07 > 0:01:12But researchers are engaged in a fight-back against the superbugs.
0:01:13 > 0:01:16Bacteria have been on the earth for billion years,
0:01:16 > 0:01:20humans have been on the earth a few hundred thousand years.
0:01:20 > 0:01:25Right so, they have the accumulated smarts of eons of generations.
0:01:25 > 0:01:28What we do have, as humans, is we have brains.
0:01:30 > 0:01:34The rise of bacteria resistant to antibiotics
0:01:34 > 0:01:38is being seen as a major public health threat.
0:01:41 > 0:01:45So scientists are devising new and sophisticated ways
0:01:45 > 0:01:47to try to defeat the superbugs.
0:02:09 > 0:02:13Professor Hazel Barton is tracking down
0:02:13 > 0:02:15one of humanity's greatest treasures.
0:02:21 > 0:02:23To find it she has to venture
0:02:23 > 0:02:26to one of the most untouched places on earth,
0:02:27 > 0:02:31hundreds of metres underground.
0:02:31 > 0:02:35It's finding a hole, nobody knows where it goes
0:02:35 > 0:02:37and you kind of push and shove your way through,
0:02:37 > 0:02:39and it's spectacular and it's beautiful
0:02:39 > 0:02:43and you're the first person to see it and you leave the first footprints.
0:02:47 > 0:02:50And so you get kind of a man in the moon feeling to be in there.
0:02:54 > 0:02:58She's hunting for something that we all take for granted.
0:03:00 > 0:03:05In these caves are tiny microbes crucial to our survival.
0:03:07 > 0:03:12Where you want to go is where you can spot bedrock
0:03:12 > 0:03:15and it's kind of dry but near enough the water that
0:03:15 > 0:03:18that organic material can leach in.
0:03:18 > 0:03:23And so somewhere like here, and you can see, this is one here.
0:03:23 > 0:03:29These little dots of white here are the colonies of microbes.
0:03:29 > 0:03:31So those are what we go in for and those are what we go after.
0:03:36 > 0:03:39These tiny microbes are incredibly precious
0:03:39 > 0:03:43because they can produce life-saving drugs we all rely on.
0:03:44 > 0:03:46Antibiotics.
0:03:47 > 0:03:51Professor Barton is going to the ends of the earth
0:03:51 > 0:03:54because here she can find new antibiotics.
0:03:55 > 0:04:01We need new ones, because the ones we have are starting to fail.
0:04:01 > 0:04:04The last thing you want to do is go to the clinic, give someone
0:04:04 > 0:04:07this drug that's gonna save their life, and it's not working.
0:04:11 > 0:04:16Scientists like Professor Barton are going to such extreme lengths
0:04:16 > 0:04:20because finding new antibiotics is fast becoming
0:04:20 > 0:04:22the most critical concern.
0:04:31 > 0:04:36Antibiotics are one of the miracles of modern medicine.
0:04:36 > 0:04:40Since the discovery of penicillin in 1928,
0:04:40 > 0:04:42they have revolutionized our lives.
0:04:48 > 0:04:50They have stopped simple cuts
0:04:50 > 0:04:53developing into life-threatening infections,
0:04:53 > 0:04:57saved millions from diseases like cholera,
0:04:57 > 0:05:00diphtheria and tuberculosis.
0:05:02 > 0:05:06Antibiotics are so valuable because they stop and destroy
0:05:06 > 0:05:10the bacteria that cause these life-threatening diseases.
0:05:12 > 0:05:16But over the last decade scientists have witnessed outbreaks
0:05:16 > 0:05:20around the world where antibiotics we have relied on in the past
0:05:20 > 0:05:22have stopped working.
0:05:23 > 0:05:28These outbreaks have been caused by new types of bacteria.
0:05:28 > 0:05:31Bacteria that can sweep straight through our antibiotics,
0:05:31 > 0:05:33and carry on growing.
0:05:35 > 0:05:37These are the superbugs.
0:05:40 > 0:05:44And we are becoming powerless against them.
0:05:44 > 0:05:46But by studying these outbreaks,
0:05:46 > 0:05:49scientists are hoping to defeat them.
0:05:54 > 0:05:58The Brooke Army Medical Centre in Texas.
0:06:01 > 0:06:06Just a few years ago, this renowned military hospital
0:06:06 > 0:06:09unexpectedly found itself at the frontline
0:06:09 > 0:06:11of the war against superbugs.
0:06:12 > 0:06:17It started in 2006 when Master Sergeant Dan Robles
0:06:17 > 0:06:20was just four months into his deployment to Iraq.
0:06:22 > 0:06:26His unit was on a routine patrol, searching for a weapons cache.
0:06:32 > 0:06:36It was about 2.00 in the afternoon, Baghdad time.
0:06:37 > 0:06:41It looked like business as usual, cars driving back and forth,
0:06:41 > 0:06:44people on the side of the streets.
0:06:44 > 0:06:46It was quiet.
0:06:50 > 0:06:55And there was just a big flash of light,
0:06:55 > 0:06:58it sounded like I had my head in a bell
0:06:58 > 0:06:59and someone was pounding on it real hard.
0:06:59 > 0:07:01There was smoke everywhere.
0:07:03 > 0:07:06The patrol had been hit by an IED
0:07:06 > 0:07:08which tore into his side of the vehicle.
0:07:12 > 0:07:15Sitting there in the Humvee after the explosion, I looked down
0:07:15 > 0:07:19and I saw that one part of my leg, my calf muscle,
0:07:19 > 0:07:22through the pants of my uniform.
0:07:22 > 0:07:25And I didn't want to look down after that.
0:07:28 > 0:07:30He sustained terrible injuries,
0:07:30 > 0:07:34and ultimately the combat medics were unable to save his legs.
0:07:39 > 0:07:44Within days, he was back on home soil at the Brooke Army Medical Centre,
0:07:44 > 0:07:47but he was about to face an even tougher battle.
0:07:51 > 0:07:57His wounds were infected and the usual antibiotics weren't working.
0:08:03 > 0:08:07So they called in the Chief of the Infectious Disease Service,
0:08:07 > 0:08:09Colonel Clint Murray.
0:08:11 > 0:08:13You're not necessarily sure who the enemy is
0:08:13 > 0:08:15when you walk in to see your patient.
0:08:15 > 0:08:18I think it's very similar to what we do in combat,
0:08:18 > 0:08:21is we try to figure out what we're doing who are we fighting?
0:08:21 > 0:08:22Why are we fighting them?
0:08:24 > 0:08:29Colonel Murray discovered that his patient had brought back from Iraq
0:08:29 > 0:08:32three of the toughest superbugs to beat.
0:08:37 > 0:08:41The first thing to do was protect the other patients
0:08:41 > 0:08:44and control the outbreak.
0:08:44 > 0:08:47So what we do is we try to isolate all our patients,
0:08:47 > 0:08:49put them in their private rooms and before we go in
0:08:49 > 0:08:51and out of those rooms, we put on gowns and gloves
0:08:51 > 0:08:53to really prevent the bacteria from getting on us
0:08:53 > 0:08:55so when we get to the next patient's room
0:08:55 > 0:08:57we're not taking the bacteria with us.
0:08:59 > 0:09:00Everyone does this,
0:09:00 > 0:09:03so you'll actually see pictures of Presidents putting this stuff on
0:09:03 > 0:09:06before they've gone into some soldier's room in the past.
0:09:06 > 0:09:07It's just what you do.
0:09:11 > 0:09:15Now he turned his attention to treating the infection,
0:09:15 > 0:09:19but his usual arsenal of antibiotics just wouldn't work.
0:09:20 > 0:09:24The number of antimicrobial agents we had were limited to treat them.
0:09:24 > 0:09:26So in contrast to giving them the standard antibiotic
0:09:26 > 0:09:30we give anyone that has a wound, we'd have to sort of
0:09:30 > 0:09:33what we call is a bigger gun, but a more powerful antibiotic.
0:09:35 > 0:09:38But these powerful antibiotics carry a risk.
0:09:40 > 0:09:45They're not just toxic to bacteria, they can be toxic to people too.
0:09:46 > 0:09:50I do remember Dr Murray explaining my situation to me,
0:09:50 > 0:09:54and I was like, "OK, let's do it, whatever we've got to do."
0:09:54 > 0:09:59Like most doctors, Colonel Murray has rarely used these antibiotics
0:09:59 > 0:10:02because of the damaging side effects.
0:10:02 > 0:10:07It had started to shut down my kidneys, I went into renal failure.
0:10:07 > 0:10:11And so he comes back and says, "We've got to stop the antibiotics."
0:10:11 > 0:10:15Based upon that, I really figured out, OK so here are the bacteria
0:10:15 > 0:10:18and here's how we're helping you, but here's how we're hurting you.
0:10:18 > 0:10:21I knew it was going to be a long fight
0:10:21 > 0:10:25when it started doing more damage than good.
0:10:27 > 0:10:30They had to keep changing the antibiotics
0:10:30 > 0:10:32as each one became too toxic.
0:10:35 > 0:10:39And this time it had shut down my immune system.
0:10:39 > 0:10:43That was probably the most scary thing ever,
0:10:43 > 0:10:44out of my whole ordeal.
0:10:44 > 0:10:49No white blood cells, no immune system.
0:10:49 > 0:10:53I had to wear a mask, I was in isolation.
0:10:53 > 0:10:59Any cold, any...you know, the simple cold could have killed me
0:10:59 > 0:11:01because I had nothing to fight it off.
0:11:04 > 0:11:08Dan Robles is living a normal life back with his family,
0:11:08 > 0:11:12but six years after the attack he still comes here
0:11:12 > 0:11:15to check on his ongoing struggle with the superbugs.
0:11:17 > 0:11:20Looking back over the two battles for his life,
0:11:20 > 0:11:24his fight with the superbugs was the toughest.
0:11:24 > 0:11:27When I was hurt, at least I knew that there was a chance
0:11:27 > 0:11:32that I could survive, and that things were in place
0:11:32 > 0:11:35to take care of me and fix me and make me better.
0:11:35 > 0:11:39But as far as losing your immune system,
0:11:39 > 0:11:44there was nothing that any doctor in the hospital could do
0:11:44 > 0:11:51to keep me from getting the simple cold that could potentially kill me.
0:11:51 > 0:11:54That was the scariest.
0:11:54 > 0:11:58And it was scary because my family was right there with me.
0:11:58 > 0:12:03And I was more worried about them watching something like that happen
0:12:03 > 0:12:07than me coming back from Iraq in a box.
0:12:10 > 0:12:13The Brooke Army Medical Centre experienced what happens
0:12:13 > 0:12:16when a superbug enters a hospital.
0:12:18 > 0:12:22Often the only choice for doctors is to use antibiotics
0:12:22 > 0:12:24which themselves can be harmful.
0:12:24 > 0:12:26The antibiotics that I could use ten years ago
0:12:26 > 0:12:28are almost completely ineffective now
0:12:28 > 0:12:30for some of the bacteria we have.
0:12:30 > 0:12:32And often times we are resorting
0:12:32 > 0:12:35to that last-ditch effort of antibiotics.
0:12:35 > 0:12:37If we don't fix this issue,
0:12:37 > 0:12:40we're eventually not going to have antibiotics.
0:12:49 > 0:12:53The reason scientists are concerned is that over the last ten years,
0:12:53 > 0:12:57antibiotic resistance has been growing across the world,
0:12:59 > 0:13:04which has forced scientists to devise new strategies to combat it.
0:13:13 > 0:13:17Dr Ruth McNerney is at the forefront of the battle against tuberculosis,
0:13:17 > 0:13:21a disease caused by bacteria we thought we'd confined to history.
0:13:24 > 0:13:26In the 18th-19th century,
0:13:26 > 0:13:29tuberculosis was the biggest killer, full stop.
0:13:29 > 0:13:31I mean, not just in infectious diseases.
0:13:33 > 0:13:37In the middle of the 19th century, life expectancy was just 41.
0:13:39 > 0:13:41In this time before antibiotics,
0:13:41 > 0:13:46diseases like TB spread through the crowded and cramped streets.
0:13:46 > 0:13:50It transmits very easily through the air
0:13:50 > 0:13:52so it's very hard to avoid getting TB,
0:13:52 > 0:13:54you don't know you've been exposed,
0:13:54 > 0:13:57you don't have to do anything to catch TB, except continue breathing.
0:13:58 > 0:14:02It would just affect everyone. Young and old.
0:14:05 > 0:14:08One of the great achievements of modern medicine
0:14:08 > 0:14:12was the defeat of this disease with a cocktail of antibiotics.
0:14:14 > 0:14:18Today, over 8 million people live in London
0:14:18 > 0:14:20without giving a thought to TB.
0:14:23 > 0:14:28But our crowded cities are still the perfect playground for bacteria.
0:14:28 > 0:14:32We pour into the city every day, we pour down the tube,
0:14:32 > 0:14:34on to buses, out round the streets.
0:14:34 > 0:14:36If someone had infectious TB,
0:14:36 > 0:14:38and they were coughing out the tiny droplets
0:14:38 > 0:14:41then it would be very easy to infect so many people.
0:14:41 > 0:14:42It would spread very, very easily.
0:14:42 > 0:14:46Now if we can imagine that we didn't have the antibiotics to treat TB,
0:14:46 > 0:14:49well, we'd be in big trouble because that's the only way
0:14:49 > 0:14:50we can stop TB spreading.
0:14:52 > 0:14:55But the fear now is that our achievement
0:14:55 > 0:14:58in controlling this disease is being threatened.
0:14:59 > 0:15:05Dr McNerney is seeing a rise in cases of antibiotic-resistant TB.
0:15:05 > 0:15:08We're now seeing the emergence of strains of TB
0:15:08 > 0:15:10that are resistant to the drugs.
0:15:10 > 0:15:13And that's becoming quite a serious problem.
0:15:13 > 0:15:16One of the issues is that we don't know how much drug resistance
0:15:16 > 0:15:18there is because it's actually quite difficult to measure.
0:15:20 > 0:15:24For now, the resistant strains showing up in the UK
0:15:24 > 0:15:28can still be treated by a small number of antibiotics.
0:15:28 > 0:15:33But outside the UK, Dr McNerney has seen a new strain of TB emerge
0:15:33 > 0:15:37that is resistant to all of the antibiotics we have to treat it.
0:15:37 > 0:15:40It could arrive tomorrow on an aeroplane. It might already be here.
0:15:40 > 0:15:43We don't know. We just have to be on our guard.
0:15:43 > 0:15:47We just can't afford to let this genie out of the bag.
0:15:56 > 0:15:59Scientists are now trying to understand
0:15:59 > 0:16:03exactly how superbugs have gained resistance,
0:16:05 > 0:16:08and, ultimately, how we can defeat them.
0:16:19 > 0:16:23Here at Harvard University,
0:16:23 > 0:16:26scientists are investigating why some of our antibiotics are failing.
0:16:31 > 0:16:37It's an experiment that happens in Professor Roy Kishony's lab.
0:16:38 > 0:16:42Here they are deliberately trying to create superbugs.
0:16:44 > 0:16:48This is a new device we've developed - we call it the morbidostat.
0:16:51 > 0:16:56Using the morbidostat, they are going to produce a highly resistant version
0:16:56 > 0:16:59of a harmless strain of a bacteria we all have in our gut.
0:16:59 > 0:17:01E. coli.
0:17:02 > 0:17:05At the beginning you have bacteria just growing
0:17:05 > 0:17:08happily in the tubes, they have enough food, they are growing fast.
0:17:11 > 0:17:14They start by trying to kill the E. coli
0:17:14 > 0:17:17by dripping in a low concentration of antibiotic.
0:17:20 > 0:17:24But as the millions of bacteria have been multiplying in the tubes,
0:17:24 > 0:17:26some, by chance, will have developed mutations
0:17:26 > 0:17:30that allow them to be resistant to the antibiotic.
0:17:30 > 0:17:34This mutant would start replicating faster than everyone else,
0:17:34 > 0:17:38ultimately it would take over on the whole population.
0:17:38 > 0:17:42So now they try to kill this new mutant strain.
0:17:43 > 0:17:46They up the strength of the antibiotic.
0:17:46 > 0:17:48Again, most of them die.
0:17:48 > 0:17:52But a new mutation appears,
0:17:52 > 0:17:55that can survive the even stronger antibiotic.
0:17:55 > 0:17:58And then we see another step, now they can grow
0:17:58 > 0:18:00in even higher drug concentrations,
0:18:00 > 0:18:04so we keep iterating this process over and over and over.
0:18:06 > 0:18:10This experiment shows that bacteria become resistant
0:18:10 > 0:18:15by being exposed to low levels of the very thing we use to protect us,
0:18:15 > 0:18:18antibiotics.
0:18:24 > 0:18:28Now the team have created a new experiment to find out exactly
0:18:28 > 0:18:33what is happening in these mutant bacteria to allow them be resistant.
0:18:38 > 0:18:42It starts with what is in effect a giant Petri dish.
0:18:44 > 0:18:47We're setting an experiment really for the first time
0:18:47 > 0:18:52in which we're going to let bacteria swim against
0:18:52 > 0:18:56an ever-increasing concentration of an antibiotic, and see what happens.
0:18:58 > 0:19:01The jelly contains food for the bacteria to grow,
0:19:01 > 0:19:05but each slab is infused with an increasing concentration
0:19:05 > 0:19:09of antibiotic, which should act as a barrier, killing the bacteria.
0:19:10 > 0:19:13First slab is no drug,
0:19:13 > 0:19:15then about the amount needed to kill the bacteria,
0:19:15 > 0:19:19then ten times more, 100 times more, and 1,000 times more.
0:19:22 > 0:19:26The experiment begins with a tiny drop of E. coli.
0:19:28 > 0:19:31They're certainly going to spread when there is no drug but
0:19:31 > 0:19:35we want to see can they actually go to the place where there is an antibiotic?
0:19:37 > 0:19:42A time-lapse camera captures the spread of the bacteria.
0:19:45 > 0:19:49As the experiment begins, it's easy for the bacteria to grow
0:19:49 > 0:19:52in the first section, with no antibiotic.
0:19:55 > 0:19:57Where there is no drug, it's very easy for them,
0:19:57 > 0:19:59there's food but no stress.
0:19:59 > 0:20:03Then they hit the boundary where the drug concentration increases.
0:20:03 > 0:20:06At the barrier where the antibiotic starts
0:20:06 > 0:20:10at the first concentration, the spread is halted.
0:20:10 > 0:20:12They get stuck there for a while,
0:20:12 > 0:20:15they try to go into this area because there is food,
0:20:15 > 0:20:18but every time they try to go into it they get killed by the drug.
0:20:21 > 0:20:24But that doesn't last long.
0:20:24 > 0:20:29Very soon, a mutant appears that can break through the barrier.
0:20:29 > 0:20:32Whole new colonies grow that can live happily
0:20:32 > 0:20:34in this concentration of antibiotic.
0:20:37 > 0:20:43And it doesn't stop there, this happens again and again,
0:20:43 > 0:20:46even up to 1,000 times concentration.
0:20:48 > 0:20:51At the end of the experiment we are the maximal level of solubility
0:20:51 > 0:20:56of the drug, we just cannot add more drug, it doesn't dissolve anymore.
0:20:57 > 0:21:00This carefully controlled epidemic
0:21:00 > 0:21:03all happens in the space of just one week.
0:21:04 > 0:21:07The team is beginning to pick apart these mutant bacteria
0:21:07 > 0:21:12to see exactly how this is happening in the presence of antibiotics,
0:21:13 > 0:21:18by peering inside the bacteria, at their genes.
0:21:18 > 0:21:19What actually happen under the hood,
0:21:19 > 0:21:22when we open and look at the genomes of this bacteria.
0:21:22 > 0:21:24We can do it now, we can sequence a whole genome of these bacteria
0:21:24 > 0:21:27and see what are the exact changes that happen.
0:21:28 > 0:21:33Typically, what genes changed and allowed them to mutate in such a way
0:21:33 > 0:21:37it can grow in this higher drug concentration.
0:21:37 > 0:21:39This is evolution in action.
0:21:42 > 0:21:48Over millions of divisions, the bacteria's DNA changes.
0:21:49 > 0:21:51Evolution happens here fairly fast,
0:21:51 > 0:21:55in basically two weeks of experiment
0:21:55 > 0:21:58we see a very dramatic increase in drug resistance,
0:21:58 > 0:22:021,000-fold increase in drug resistance.
0:22:02 > 0:22:05So, yes, you might want to say evolution is happening
0:22:05 > 0:22:09in front of our eyes, as we speak.
0:22:09 > 0:22:14Used properly, antibiotics can kill bacteria and save lives,
0:22:16 > 0:22:19but as these experiments show,
0:22:19 > 0:22:24low levels of antibiotics encourage bacteria to develop resistance.
0:22:26 > 0:22:28In the real world too,
0:22:28 > 0:22:33our use of antibiotics may actually be causing more superbugs to emerge.
0:22:41 > 0:22:44Superbugs were once rare and infrequent,
0:22:44 > 0:22:47but they are now showing up across the world's major cities.
0:22:51 > 0:22:55Professor Tim Walsh studies these newly emerging outbreaks,
0:22:55 > 0:23:00and there's one region that concerns him most of all.
0:23:00 > 0:23:03The southern Asian continent suffers from antibiotic resistance
0:23:03 > 0:23:06far more than probably any other area on the planet.
0:23:08 > 0:23:11For the last three years he's been travelling to Southern Asia
0:23:11 > 0:23:15to understand why some of the poorest parts of the planet
0:23:15 > 0:23:18are superbug hotspots.
0:23:26 > 0:23:30He's on his way to Karachi's Civil Hospital, in Pakistan.
0:23:33 > 0:23:36In both rich and poor countries,
0:23:36 > 0:23:41resistant bacteria cause their most costly and deadly infections
0:23:41 > 0:23:46in the places where people are most vulnerable - hospitals.
0:23:48 > 0:23:51The doctors at the hospital are working with Prof Walsh
0:23:51 > 0:23:57to identify and improve the conditions contributing to the spread of superbugs.
0:23:57 > 0:24:00A lot of times you see them and they're not washing their hands.
0:24:00 > 0:24:03This is one of the reasons we have so much infection.
0:24:03 > 0:24:06I think the infection control issue here
0:24:06 > 0:24:08clearly seems to be very important.
0:24:08 > 0:24:12One of the key issues in places like the Civil Hospital
0:24:12 > 0:24:16is sort of overcrowding of the wards and lack of infection control.
0:24:17 > 0:24:20Windows are open so bacteria can kind of blow into
0:24:20 > 0:24:25intensive care units etc, and there seems to be a lack of
0:24:25 > 0:24:29understanding as to the importance of things like hand-washing
0:24:29 > 0:24:33in moving from patient to patient, or indeed from ward to ward.
0:24:35 > 0:24:38The doctors are facing dangerous infections,
0:24:38 > 0:24:40in impossible conditions.
0:24:40 > 0:24:42Professor Walsh has found
0:24:42 > 0:24:44there are no dedicated infection control teams,
0:24:44 > 0:24:49insufficient bacterial diagnosis, and no isolation rooms.
0:24:52 > 0:24:56Well, the people in Karachi know about their limitations,
0:24:56 > 0:24:59and that's the great thing, they're very open and honest about them,
0:24:59 > 0:25:02they realise they must do something about it.
0:25:03 > 0:25:07But there's another factor at play that the hospital can't control.
0:25:07 > 0:25:09There is an easy availability
0:25:09 > 0:25:12of the very thing needed to create superbugs.
0:25:19 > 0:25:24In most parts of Asia, antibiotics can be purchased
0:25:24 > 0:25:27freely from shops without prescription.
0:25:27 > 0:25:30A problem that the doctors throughout the hospital
0:25:30 > 0:25:32are aware of.
0:25:32 > 0:25:34From the pharmacy right outside the hospital
0:25:34 > 0:25:38I bought all these antibiotics and they cost me just 2.50 rupees.
0:25:38 > 0:25:42Anyone can go and buy these.
0:25:42 > 0:25:47Bought over the counter, antibiotics are misused and misunderstood,
0:25:47 > 0:25:50taken even for things that they can't cure.
0:25:52 > 0:25:55And there are no instructions, certainly not with these, on usage.
0:25:55 > 0:25:58Yeah, they don't come with a leaflet.
0:25:58 > 0:26:02And a lot of people just will go to the corner shop
0:26:02 > 0:26:06and simply buy a whole range of antibiotics and simply self medicate
0:26:06 > 0:26:10and you can see on this one here one tablet has obviously been sold
0:26:10 > 0:26:14to one particular person - just to take one tablet is just crazy.
0:26:14 > 0:26:17You're just exposing the bacteria to what we call
0:26:17 > 0:26:21sub-killing-concentrations of that antibiotic.
0:26:21 > 0:26:24And so you're actually not killing the bacteria, or indeed
0:26:24 > 0:26:28preventing it from growing, and more or less all we're doing
0:26:28 > 0:26:29to the bacteria is saying,
0:26:29 > 0:26:33"OK, here's the antibiotic, become resistant."
0:26:35 > 0:26:38It's not just the sale of antibiotics that's unregulated.
0:26:42 > 0:26:45Elsewhere in Asia, outlets from the industrial-scale manufacture
0:26:45 > 0:26:50of antibiotics have contaminated rivers and streams.
0:26:54 > 0:26:59As a result, societies can be awash with antibiotics,
0:26:59 > 0:27:02the perfect conditions for superbugs.
0:27:03 > 0:27:07However, the conditions needed to create a superbug
0:27:07 > 0:27:11are not just happening in Asia, but right across the world.
0:27:16 > 0:27:19Professor Lance Price is a superbug tracker.
0:27:21 > 0:27:25A few years ago, he was called to investigate a superbug
0:27:25 > 0:27:29which helped to reveal how another use of antibiotics
0:27:29 > 0:27:31was driving resistance.
0:27:33 > 0:27:38Bacteria are everywhere. They're a natural part of our environment,
0:27:38 > 0:27:43they're a natural part of us, in fact human beings are sort of
0:27:43 > 0:27:46a walking ecosystem, we have bacteria that live in and on us,
0:27:46 > 0:27:51one of the bacteria that I'm particularly interested in
0:27:51 > 0:27:53is Staph aureus.
0:27:53 > 0:27:57It's estimated the between 20% and 30% of humans
0:27:57 > 0:27:59are colonised with Staph aureus,
0:27:59 > 0:28:02and most of the time it doesn't pose a problem.
0:28:04 > 0:28:07If Staph aureus does cause an infection, it is usually
0:28:07 > 0:28:11straightforward to treat with an antibiotic called methicillin.
0:28:14 > 0:28:18But when it develops resistance to methicillin
0:28:18 > 0:28:21it becomes a superbug we've all heard of, MRSA.
0:28:23 > 0:28:26This is a picture of methicillin-resistant Staph aureus.
0:28:26 > 0:28:29Methicillin-resistant Staph aureus and regular Staph aureus
0:28:29 > 0:28:31don't look any different in a photo like this,
0:28:31 > 0:28:35but when you look at the DNA, you'll see very distinct differences.
0:28:35 > 0:28:39MRSA carries genes that make it resistant to methicillin,
0:28:39 > 0:28:43that's why we call it methicillin-resistant Staph aureus, or MRSA.
0:28:44 > 0:28:47He uses these genetic differences as clues
0:28:47 > 0:28:49to lead him to the source of the outbreaks.
0:28:49 > 0:28:53We crack these cells open and we sequence the DNA,
0:28:53 > 0:28:57and then we use that to trace the evolutionary history of these bugs
0:28:57 > 0:29:00and determine how and sometimes when
0:29:00 > 0:29:02they became resistant to methicillin.
0:29:06 > 0:29:11Three years ago, he discovered a new strain of MRSA
0:29:11 > 0:29:15in 18 different countries, including the USA and in Europe.
0:29:16 > 0:29:20And there was one thing that seemed to connect them all.
0:29:20 > 0:29:24A new strain of MRSA emerged that we'd never seen before,
0:29:24 > 0:29:27and when we started tracking it back we found out that
0:29:27 > 0:29:31most of the people who were getting it were actually employed in the
0:29:31 > 0:29:35livestock industry, so people that had direct exposure to food animals.
0:29:35 > 0:29:39And that set off an investigation for us.
0:29:39 > 0:29:42The genetic trail revealed this strain of MRSA
0:29:42 > 0:29:46had passed into these people from pigs.
0:29:47 > 0:29:50But then they went further.
0:29:50 > 0:29:54They tried to follow the genes back to a time before
0:29:54 > 0:29:56the MRSA became resistant.
0:29:56 > 0:29:59And what we found was a big surprise to us,
0:29:59 > 0:30:04we found that in fact that this new strain had started off in people
0:30:04 > 0:30:08but it was not MRSA, it was just Staph aureus, or SA,
0:30:08 > 0:30:14it spread to pigs, and that's where it became resistant to methicillin.
0:30:17 > 0:30:21Professor Price had discovered that this ordinary Staph aureus bacteria
0:30:21 > 0:30:25had mutated while it was in the livestock,
0:30:25 > 0:30:27to become potentially deadly.
0:30:30 > 0:30:34To him, the reason was obvious, antibiotics.
0:30:35 > 0:30:38The simplest explanation is that we're using
0:30:38 > 0:30:41lots and lots of antibiotics in food animal production.
0:30:41 > 0:30:44Most of the time they're just being added to animal feed,
0:30:44 > 0:30:48so they're being mixed in giant silos of feed
0:30:48 > 0:30:53and given on a routine basis, just basically with every meal
0:30:53 > 0:30:56that animals are getting a little bit of antibiotics.
0:30:56 > 0:30:58Many farmers thought it was the best way
0:30:58 > 0:31:01to keep closely packed animals healthy
0:31:01 > 0:31:04and for them to grow faster,
0:31:04 > 0:31:07but Professor Price believes the superbug he was tracking
0:31:07 > 0:31:11was created as a result of this kind of antibiotic use.
0:31:11 > 0:31:14We're raising animals under the conditions that we know
0:31:14 > 0:31:17lead to the spread of bacteria between people,
0:31:17 > 0:31:20and then we add the magic ingredient which is antibiotics,
0:31:20 > 0:31:22which just virtually guarantees that we're going to have
0:31:22 > 0:31:23drug-resistant bacteria.
0:31:23 > 0:31:29In 2006, the European Union banned the use of antibiotics
0:31:29 > 0:31:32as growth promoters in animal feed.
0:31:32 > 0:31:37But elsewhere in the world, it is still being used in vast quantities.
0:31:37 > 0:31:41In the United States we use 29 million pounds of antibiotics
0:31:41 > 0:31:43every year in food animal production.
0:31:43 > 0:31:47I mean, you know, these are the crown jewels of modern medicine,
0:31:47 > 0:31:49they're being used like cheap production tools.
0:31:52 > 0:31:57There is a movement in the US to change this practice.
0:31:57 > 0:32:00Professor Price is working with farmers who are trying new ways
0:32:00 > 0:32:01of keeping animals healthy,
0:32:01 > 0:32:05without constant use of antibiotics in the feed.
0:32:05 > 0:32:09- Like to come in and see what we're doing here?- I would.
0:32:09 > 0:32:13Yeah. Give you some coveralls and some booties for you.
0:32:14 > 0:32:18Removing antibiotics from the feed means farmers need to take
0:32:18 > 0:32:22other measures to avoid their livestock getting infections.
0:32:22 > 0:32:25I have to wear these in a lab sometimes.
0:32:25 > 0:32:28In that case, we're protecting ourselves from the microbes
0:32:28 > 0:32:31rather than the turkeys from us.
0:32:31 > 0:32:34But working this way means farms are less likely
0:32:34 > 0:32:38to encourage superbugs to emerge.
0:32:38 > 0:32:39Everybody would say,
0:32:39 > 0:32:43"There's no way you're going to be able to grow turkeys without antibiotics."
0:32:43 > 0:32:45So we started trials and learned from that,
0:32:45 > 0:32:48that we needed to give the birds more space
0:32:48 > 0:32:52and really go out of your way to have the best animal husbandry,
0:32:52 > 0:32:54that they don't get stressed.
0:32:54 > 0:32:58And now, if we do get a sick flock, which is rare,
0:32:58 > 0:33:00but if we get one and we have to treat it,
0:33:00 > 0:33:03we can use the simplest antibiotic like a tetracycline,
0:33:03 > 0:33:05and it usually works great.
0:33:08 > 0:33:14For where it continues, large-scale use of antibiotics in animal feed
0:33:14 > 0:33:17can create the right environment for superbug emergence.
0:33:20 > 0:33:22Bacteria don't wear lapel pins.
0:33:22 > 0:33:24They're not confined to any geographic area,
0:33:24 > 0:33:29and so what we do here in the United States can potentially impact you.
0:33:29 > 0:33:33So as we create these multi-drug-resistant pathogens,
0:33:33 > 0:33:36those pathogens can then spread around the world.
0:33:36 > 0:33:39And so you should just be as concerned as I am
0:33:39 > 0:33:40about what we're doing over here.
0:33:47 > 0:33:51Wherever a superbug outbreak occurs in the world,
0:33:51 > 0:33:55doctors across the globe start to worry,
0:33:55 > 0:33:57because regardless of where they first emerge,
0:33:57 > 0:34:01a superbug can soon become a citizen of the world.
0:34:02 > 0:34:06We carry about 100 trillion bacteria in us,
0:34:06 > 0:34:09therefore, when we travel the world, they travel the world.
0:34:09 > 0:34:12Any types of resistance that occurs in one country
0:34:12 > 0:34:16can very easily be transported around the world, almost in real time.
0:34:19 > 0:34:22With the rising levels of air travel,
0:34:22 > 0:34:25resistant bacteria have hitched rides across the globe.
0:34:25 > 0:34:28Probably in about the last 15 to 20 years,
0:34:28 > 0:34:31we've managed to contaminate the whole of the planet.
0:34:31 > 0:34:34If you go to the north of Norway, or even down into Australia,
0:34:34 > 0:34:37down to Tasmania, you will find these type of resistances.
0:34:38 > 0:34:42Not only are superbugs being found all over the world,
0:34:42 > 0:34:45scientists are finding that these bacteria
0:34:45 > 0:34:47are becoming harder and harder to treat.
0:34:51 > 0:34:56It's this problem that Professor Tim Walsh grapples with every day.
0:34:56 > 0:35:00This a very quick illustration of how resistance has evolved
0:35:00 > 0:35:02over about the last 20 years.
0:35:04 > 0:35:08Each white disc on these plates contains a different antibiotic.
0:35:10 > 0:35:14A clear circle indicates the antibiotic is working
0:35:14 > 0:35:16and killing the bacteria.
0:35:18 > 0:35:21This E. coli from India about 20 years ago
0:35:21 > 0:35:24is fully sensitive to the series of antibiotics
0:35:24 > 0:35:28which we would use to treat E. coli infections.
0:35:30 > 0:35:3312 years ago, the E. coli had started to become resistant
0:35:33 > 0:35:36to some of the antibiotics,
0:35:36 > 0:35:41but the newest strain has shown unprecedented levels of resistance.
0:35:42 > 0:35:45You can see here it's virtually totally resistant.
0:35:45 > 0:35:48The only antibiotic that shows any activity
0:35:48 > 0:35:51against this particular organism, is this antibiotic here,
0:35:51 > 0:35:53which has some issues with toxicity,
0:35:53 > 0:35:57and it's at the moment about 40, 50 years old.
0:35:57 > 0:35:59We're starting to have a bit of a renaissance with it,
0:35:59 > 0:36:02because clearly you can see that we have nothing left.
0:36:02 > 0:36:06We are beginning to see this level of resistance appear
0:36:06 > 0:36:08all over the world.
0:36:09 > 0:36:14Bacteria that only respond to a few rarely used antibiotics.
0:36:15 > 0:36:17And the trouble is,
0:36:17 > 0:36:22these antibiotics of last resort can often be toxic themselves.
0:36:24 > 0:36:27Scientists believe there is an urgent need
0:36:27 > 0:36:30to re-stock our arsenal with new antibiotics.
0:36:49 > 0:36:55It's a hunt that has taken Professor Hazel Barton across the globe.
0:37:00 > 0:37:04I get to travel the world, I get to see amazing things,
0:37:04 > 0:37:05so I just love it!
0:37:07 > 0:37:10You might think that new antibiotics were created in a lab,
0:37:10 > 0:37:14or discovered deep in the rainforest,
0:37:14 > 0:37:18but actually most of them have been found in the dirt.
0:37:19 > 0:37:23Almost all of the antibiotics that we use now
0:37:23 > 0:37:25have come from soil micro-organisms.
0:37:25 > 0:37:29The procedures that we have in the lab for finding antibiotics
0:37:29 > 0:37:33is literally to pull the microbes out of this dirt and grow them.
0:37:34 > 0:37:38More than three-quarters of the antibiotics we regularly use
0:37:38 > 0:37:41in hospitals today were taken from microbes in the soil.
0:37:45 > 0:37:47And the trouble is, we've been doing that for 50 years
0:37:47 > 0:37:49and we keep finding the same things.
0:37:51 > 0:37:56And the best microbes for producing antibiotics are bacteria themselves.
0:37:58 > 0:38:03To find new antibiotics, Professor Barton has to hunt down new bacteria
0:38:03 > 0:38:07in some of the most untouched places on Earth.
0:38:08 > 0:38:11Hundreds of metres underground.
0:38:30 > 0:38:32Oh, it's slippery here.
0:38:34 > 0:38:35For bacteria,
0:38:35 > 0:38:39these caves are one of the toughest places in the world to survive.
0:38:42 > 0:38:45Between where we're standing right now and the surface,
0:38:45 > 0:38:47there's about 1,000 feet of rock.
0:38:49 > 0:38:52So for anything that's happening on the surface,
0:38:52 > 0:38:56all that energy from plants and animals, for that to come here,
0:38:56 > 0:39:01it has to get through all that rock, and it can't do that very easily.
0:39:02 > 0:39:05So we end up with a very starved environment,
0:39:05 > 0:39:09where there's hardly any energy available.
0:39:09 > 0:39:12These caves may look peaceful and still,
0:39:12 > 0:39:16but they are, in fact, a battlefield.
0:39:16 > 0:39:19With so few resources available,
0:39:19 > 0:39:22bacteria must fight each other to survive.
0:39:26 > 0:39:31They become either much more careful of their resources
0:39:31 > 0:39:32in defending them,
0:39:32 > 0:39:37or they get a lot more aggressive in stealing someone else's resources.
0:39:38 > 0:39:42They do this by producing an arsenal of chemical weapons.
0:39:44 > 0:39:47Professor Barton has been collecting these weapons
0:39:47 > 0:39:51in the hope they might be used as antibiotics.
0:39:52 > 0:39:55Last year, she captured one type of bacteria
0:39:55 > 0:40:01that produced over 38 different bacteria-killing chemicals.
0:40:01 > 0:40:03To put that in perspective,
0:40:03 > 0:40:08there's only about 40 antimicrobial drugs in the clinic right now.
0:40:08 > 0:40:11So one bug from this cave was able to make
0:40:11 > 0:40:15almost as many as we have available to us in the clinic.
0:40:15 > 0:40:18Not all of those are going to be useful as medicines,
0:40:18 > 0:40:20but the potential becomes huge.
0:40:20 > 0:40:24I mean, we've pulled out 4,000 microbes,
0:40:24 > 0:40:26so it's almost like a chemical universe
0:40:26 > 0:40:30and we are kind of playing on the edges of it
0:40:30 > 0:40:33with antimicrobial compounds and there's this huge vast
0:40:33 > 0:40:38unknown space that we've yet to kind of explore to see what's out there.
0:40:40 > 0:40:43The work of scientists like Professor Barton
0:40:43 > 0:40:47is becoming increasingly important, as any new antibiotic discovery
0:40:47 > 0:40:52will enable us to retain our hold over the superbugs.
0:40:53 > 0:40:58But eventually, bacteria will always find a way to become resistant
0:40:58 > 0:41:01to even the new antibiotics.
0:41:04 > 0:41:07If we are going to finally overcome the problem of resistance
0:41:07 > 0:41:10we are going to need a whole new approach.
0:41:29 > 0:41:32On the face of it, this seems an unlikely place to discover
0:41:32 > 0:41:36a new strategy for fighting superbugs.
0:41:36 > 0:41:41It's a sewage works in Buckinghamshire.
0:41:41 > 0:41:45But microbiologist Dr David Harper believes the answer
0:41:45 > 0:41:48may be found here.
0:41:48 > 0:41:52He's hoping to exploit the weapons technology of a creature
0:41:52 > 0:41:55that has developed its own way to fight bacteria.
0:41:57 > 0:42:01Bacteria have been on the Earth for billions of years.
0:42:01 > 0:42:03That's why they're so tricky.
0:42:03 > 0:42:05But there's something else that's been on the Earth
0:42:05 > 0:42:06for billions of years.
0:42:06 > 0:42:09And it knows how to deal with bacteria.
0:42:09 > 0:42:10That's what I'm here to collect.
0:42:10 > 0:42:15- Good to see you.- And you, David. - Let's go and get some good ones.
0:42:16 > 0:42:20Raw sewage is the perfect breeding ground for bacteria.
0:42:22 > 0:42:24But that also makes it the ideal home
0:42:24 > 0:42:26for the ultimate bacterial predator.
0:42:28 > 0:42:33He wants to enlist that predator to fight for us in the superbug war.
0:42:33 > 0:42:37In there, although we can't see it, there's a war going on.
0:42:37 > 0:42:41There are billions of bacteria struggling for existence,
0:42:41 > 0:42:44and tens of billions of bacteriophages.
0:42:44 > 0:42:49Viruses that only and specifically affect and kill bacteria.
0:42:49 > 0:42:53And they are fighting in there, as we speak.
0:42:54 > 0:42:59Just like humans, bacteria can be infected and killed by viruses.
0:42:59 > 0:43:04Bacteriophages are the most common and diverse predators on Earth.
0:43:06 > 0:43:10There are 10,000 billion, billion, billion,
0:43:10 > 0:43:12bacteriophages on the planet.
0:43:12 > 0:43:14We haven't actually counted, that is an estimate.
0:43:16 > 0:43:19Dr Harper wants to get these bacterial viruses
0:43:19 > 0:43:23fighting on our side in the superbug war.
0:43:23 > 0:43:29"Bacteriophage" literally means "bacteria eater".
0:43:29 > 0:43:32They work by landing on the bacteria,
0:43:32 > 0:43:35injecting in their own DNA,
0:43:35 > 0:43:39then reproducing themselves inside the bacteria until it bursts.
0:43:42 > 0:43:45Back in his company's lab,
0:43:45 > 0:43:47Dr Harper is attempting to harness the power
0:43:47 > 0:43:50of these bacterial predators.
0:43:50 > 0:43:53It's a tricky business.
0:43:53 > 0:43:55To kill disease-causing bacteria,
0:43:55 > 0:44:00you need the particular phage which attacks that bacteria species.
0:44:00 > 0:44:05We go and collect the sewage, we bring it back here,
0:44:05 > 0:44:12we put the sewage into a culture of the target bacterial species.
0:44:12 > 0:44:14There are lots of different phages in there,
0:44:14 > 0:44:17I said there were billions - there are. Maybe thousands,
0:44:17 > 0:44:20maybe hundreds, will hit that particular species.
0:44:20 > 0:44:25In a few cases, you might have a species where only a few will hit it,
0:44:25 > 0:44:29but still, if they're there, they will bind,
0:44:29 > 0:44:32they will kill, they will multiply
0:44:32 > 0:44:34and you can pick them and grow them.
0:44:40 > 0:44:42Using viruses to kill bacteria
0:44:42 > 0:44:44sounds like an attractive idea in principle,
0:44:44 > 0:44:50but in practice, working with live organisms has proven difficult.
0:44:52 > 0:44:56But Dr Harper is drawn to this field of research
0:44:56 > 0:45:00because phages offer one significant advantage over antibiotics.
0:45:03 > 0:45:06Antibiotics can't change.
0:45:06 > 0:45:08If the bacteria generate resistance, that's it,
0:45:08 > 0:45:09you need a new antibiotic.
0:45:09 > 0:45:12With phages, the bacteria are their lunch.
0:45:12 > 0:45:17If they can't multiply, they die out. If they can, they grow.
0:45:17 > 0:45:21So when the bacteria change, a few phages will be in there,
0:45:21 > 0:45:23which can grow in the new ones.
0:45:23 > 0:45:28That mutation is then preferred, those phages will multiply
0:45:28 > 0:45:30and come to dominate.
0:45:30 > 0:45:34The bacteria will change again, a few of those will be able to grow,
0:45:34 > 0:45:37they grow again, they amplify, they come to dominate.
0:45:37 > 0:45:38It's an arms race.
0:45:41 > 0:45:45Tapping into this arms race would hand us a key advantage
0:45:45 > 0:45:49because the bacteriophages are able to evolve.
0:45:50 > 0:45:53If we are able to enlist them to fight for us,
0:45:53 > 0:45:58they will keep fighting for us, even as the bacteria change.
0:45:58 > 0:46:03They are in many ways a perfect drug, in many ways they aren't.
0:46:03 > 0:46:07One of the most telling things against bacteriophages as drugs
0:46:07 > 0:46:10is that nobody has yet developed one.
0:46:14 > 0:46:18Dr Harper's company have seen some early successes
0:46:18 > 0:46:21and are now planning a trial to treat lung infections
0:46:21 > 0:46:25often affecting cystic fibrosis sufferers.
0:46:27 > 0:46:32We hope that the results in cystic fibrosis will be convincing.
0:46:32 > 0:46:35We hope to move on to the large clinical trials
0:46:35 > 0:46:38of hundreds of patients, which will underpin
0:46:38 > 0:46:43progressing this to market to improve people's lives, to save people's lives.
0:46:43 > 0:46:46There's a long way still to go, but we're working on it.
0:46:49 > 0:46:54Right now, phage medicines are still in the very early stages
0:46:58 > 0:47:01but new developments in understanding exactly how
0:47:01 > 0:47:05bacteria become deadly are giving hope that there could be
0:47:05 > 0:47:06another way to outsmart them.
0:47:10 > 0:47:13Princeton University in New Jersey.
0:47:16 > 0:47:19Here, a team are taking a radically new approach,
0:47:21 > 0:47:24one that has led to an unexpected breakthrough
0:47:24 > 0:47:27in the fight against deadly bacteria.
0:47:31 > 0:47:34Professor Bonnie Bassler has spent her career
0:47:34 > 0:47:37getting in to their world.
0:47:41 > 0:47:44I love bacteria. I think most of the things
0:47:44 > 0:47:47they do on this earth are fantastic and essential,
0:47:47 > 0:47:52but bacteria have features, bells and whistles, different processes,
0:47:52 > 0:47:56that they are, that they have for fighting in their own environments.
0:47:56 > 0:48:00And when those get unleashed in a human or in an animal
0:48:00 > 0:48:02or in a plant, it can kill us.
0:48:03 > 0:48:07With antibiotics, we have been attacking bacteria,
0:48:07 > 0:48:09forcing them to evolve resistance.
0:48:11 > 0:48:15But Professor Bassler thinks that we may not have to be so aggressive.
0:48:15 > 0:48:18Instead of just smashing them to smithereens
0:48:18 > 0:48:21like we've done with traditional antibiotics, if we could learn enough
0:48:21 > 0:48:26of their secrets, and get them to spill their guts a little bit
0:48:26 > 0:48:31and tell us how they work, we could just get them to behave.
0:48:31 > 0:48:35And do behaviour modification instead of killing them.
0:48:36 > 0:48:41Compared to us, bacteria are so incredibly small
0:48:41 > 0:48:44that on their own, they shouldn't be able to hurt us at all.
0:48:46 > 0:48:49If one or a few bacteria release
0:48:49 > 0:48:53their mostly deadly arsenal of toxins, they have no effect.
0:48:53 > 0:48:56I mean, this is not a David and Goliath, this is like
0:48:56 > 0:48:58way beyond that, so the question is,
0:48:58 > 0:49:01how can these bacteria have us on our knees,
0:49:01 > 0:49:05right, how can it be that they can actually kill us?
0:49:07 > 0:49:10Bacteria don't attempt to attack us on their own,
0:49:10 > 0:49:15they wait until there are enough of them and then act all at once.
0:49:15 > 0:49:20You can think of the bacteria, each individual bacterium as a soldier,
0:49:20 > 0:49:24and so you have these masses of soldiers, but it's only useful
0:49:24 > 0:49:29when somebody says "charge", right, so the question is
0:49:29 > 0:49:35what's the information that tells the bacteria now is the time to attack?
0:49:37 > 0:49:41If we could find a way to stop the bacteria attacking together,
0:49:41 > 0:49:43they wouldn't be able to harm us.
0:49:45 > 0:49:50But understanding how they co-ordinate their attack
0:49:50 > 0:49:52is incredibly difficult
0:49:52 > 0:49:55because bacteria are hidden from sight.
0:49:55 > 0:49:59But there is a type of bacteria that you can see,
0:49:59 > 0:50:03and they have a rather unusual relationship.
0:50:11 > 0:50:15The Hawaiian bob-tailed squid is a master of disguise.
0:50:15 > 0:50:21In the day, it disappears into the sea bed,
0:50:21 > 0:50:26but when it comes out to feed at night, it's even more ingenious.
0:50:29 > 0:50:31At night, this is like the stealth bomber of the ocean,
0:50:31 > 0:50:34it likes to cloak itself in an invisible device.
0:50:34 > 0:50:35If it were to just swim around,
0:50:35 > 0:50:38the starlight or moonlight would hit its back
0:50:38 > 0:50:42and it would cast a shadow on the sea floor here
0:50:42 > 0:50:44and then predators that could see that shadow
0:50:44 > 0:50:46could calculate its trajectory, and eat it.
0:50:48 > 0:50:50To eliminate their shadow,
0:50:50 > 0:50:55these squid project light down onto the sea floor.
0:50:55 > 0:50:59So by matching how much starlight or moonlight hits its back
0:50:59 > 0:51:03with how much light comes out of its body, there's no shadow.
0:51:03 > 0:51:08So it's a fantastic sleight of hand, sleight of tentacle,
0:51:08 > 0:51:12if you will, it's a fantastic anti-predation device
0:51:12 > 0:51:15because it makes it invisible at night.
0:51:16 > 0:51:22And this incredible invisibility cloak is created by bacteria.
0:51:22 > 0:51:26There's a bacterium that lives in the body of the squid,
0:51:26 > 0:51:31the bacterium's name is Vibrio ficheri, and it makes light,
0:51:31 > 0:51:33so the squid gives the bacterium a home,
0:51:33 > 0:51:36the bacterium gives the squid light,
0:51:36 > 0:51:39and the squid uses the light to protect itself from predators.
0:51:46 > 0:51:50But just as a single dangerous bacteria would not be enough
0:51:50 > 0:51:55to make us sick, a single glowing bacteria would never produce
0:51:55 > 0:51:58enough light to help the squid.
0:51:58 > 0:52:01For the bacteria to be useful, there must be lots of them.
0:52:02 > 0:52:06So the bacteria wait until there are enough of them,
0:52:06 > 0:52:11and only then, all start glowing at exactly the same time.
0:52:11 > 0:52:13When this was initially discovered,
0:52:13 > 0:52:18the idea that bacteria could do something as a group was revelatory.
0:52:21 > 0:52:23The bacteria were working together,
0:52:23 > 0:52:27but the question was, how were they doing it?
0:52:28 > 0:52:33The beauty of these marine bacteria is that they glow in the dark,
0:52:33 > 0:52:38so they could experiment to see what exactly caused them
0:52:38 > 0:52:39to start making light.
0:52:42 > 0:52:47They discovered the bacteria were producing a chemical messenger -
0:52:47 > 0:52:50they were talking to each other.
0:52:50 > 0:52:52As they grow and divide,
0:52:52 > 0:52:55they all make and release these molecules.
0:52:55 > 0:52:59When there's more cells, the molecule outside the cells
0:52:59 > 0:53:01increases in proportion to cell number.
0:53:01 > 0:53:04And when the molecule hits a certain amount,
0:53:04 > 0:53:07the bacteria have receptors on their surfaces, they detect that the
0:53:07 > 0:53:11molecule is there and then they all change their behaviour in unison.
0:53:15 > 0:53:19Using these molecules, the bacteria were able to detect
0:53:19 > 0:53:22when other bacteria were around them.
0:53:23 > 0:53:26And by communicating with each other, the bacteria were able to
0:53:26 > 0:53:31achieve something they could never achieve as individuals.
0:53:31 > 0:53:34This behaviour is called quorum sensing.
0:53:34 > 0:53:38Sometimes, the way I think of it, is if you want to move a piano
0:53:38 > 0:53:42from over there, to over there, you don't try to do that yourself,
0:53:42 > 0:53:44you get all your friends, everybody grabs and you say,
0:53:44 > 0:53:46"One, two, three, lift."
0:53:46 > 0:53:51And then you can carry out this task as a co-ordinated synchronous group
0:53:51 > 0:53:55that you couldn't do, if you were just acting on your own.
0:54:02 > 0:54:07Once they'd discovered the glowing bacteria could talk to each other
0:54:07 > 0:54:10using chemicals, Professor Bassler began to wonder if this was the way
0:54:10 > 0:54:15dangerous bacteria were coordinating their attack.
0:54:17 > 0:54:21And so I thought, "Well, I wonder if anybody else makes this molecule."
0:54:21 > 0:54:25So I just collected every bacterium I could get my hands on.
0:54:33 > 0:54:37And every bacterium I tried that with, it worked.
0:54:37 > 0:54:40And there was this moment, I still get goose pimples with that,
0:54:40 > 0:54:42there's this moment where I thought,
0:54:42 > 0:54:45"Holy cow, they're talking between species,
0:54:45 > 0:54:47"they all make this molecule."
0:54:50 > 0:54:56It looked like all bacteria could communicate using these molecules.
0:54:56 > 0:54:59This had incredible implications.
0:54:59 > 0:55:01If she could interrupt these conversations,
0:55:01 > 0:55:05she could get the bacteria to stop their group behaviour.
0:55:05 > 0:55:07We know what these molecules are, at least some of them,
0:55:07 > 0:55:11these quorum-sensing molecules, so we've made antagonists, right,
0:55:11 > 0:55:13molecules that look kind of like the real things,
0:55:13 > 0:55:15but they jam the receptors.
0:55:15 > 0:55:18And so if you add those, it's like static, you know,
0:55:18 > 0:55:21you add these anti-quorum-sensing molecules, the bacteria can't hear.
0:55:25 > 0:55:27Professor Bassler had found a way
0:55:27 > 0:55:31to stop the glow-in-the-dark bacteria from talking.
0:55:31 > 0:55:34Could she do the same with dangerous bacteria
0:55:34 > 0:55:37and prevent them from launching their attacks?
0:55:38 > 0:55:42We started this work with Vibrio haveri and Vibrio ficheri,
0:55:42 > 0:55:45these beautiful bio-luminescent bacteria,
0:55:45 > 0:55:49but they have a nasty cousin, Vibrio cholera.
0:55:49 > 0:55:53Those two bacteria make this beautiful light, this guy kills you.
0:55:55 > 0:55:58Although completely eradicated in the UK,
0:55:58 > 0:56:02the cholera bacteria is responsible for over 100,000 deaths
0:56:02 > 0:56:05in the developing world every year.
0:56:05 > 0:56:07So we transferred what we learned
0:56:07 > 0:56:11from the glow-in-the-dark bacterium to this bacterium.
0:56:11 > 0:56:16Professor Bassler can measure the level of a protein
0:56:16 > 0:56:19that cholera bacteria produce that makes them deadly.
0:56:19 > 0:56:21This is the protein that cholera makes
0:56:21 > 0:56:23that lets it adhere to your intestine.
0:56:23 > 0:56:26It has to make this. It's step one in the infection
0:56:26 > 0:56:28and that makes it virulent.
0:56:28 > 0:56:31So then what we did was, we added our anti-quorum-sensing molecule
0:56:31 > 0:56:34at different amounts to cholera cells,
0:56:34 > 0:56:36and if we add more and more and more of our molecule,
0:56:36 > 0:56:37what you can see is,
0:56:37 > 0:56:42it makes cholera incapable of making that virulence protein,
0:56:42 > 0:56:44and incapable of making an infection.
0:56:48 > 0:56:52This is just the beginning for Professor Bassler and her team,
0:56:52 > 0:56:56as other researchers around the world are now investigating
0:56:56 > 0:56:58whether this method of silencing the bacteria
0:56:58 > 0:57:02has the potential to work where antibiotics are failing.
0:57:19 > 0:57:24Scientists have entered a new stage in the battle with superbugs.
0:57:27 > 0:57:30It may be that we have underestimated our enemy.
0:57:32 > 0:57:34They're probably smarter than I am.
0:57:34 > 0:57:36They're able to adjust fire much quicker than I can
0:57:36 > 0:57:39so they're able to develop resistance a whole lot faster
0:57:39 > 0:57:40than I can develop an antibiotic.
0:57:46 > 0:57:49But around the world, scientists are taking up
0:57:49 > 0:57:51this cat and mouse challenge.
0:57:53 > 0:57:58It is a game. They're playing their game and we need to play our game.
0:57:58 > 0:58:01We each need to do our best move.
0:58:05 > 0:58:08We are understanding bacteria better than ever before
0:58:10 > 0:58:14but maybe we don't have to triumph over all,
0:58:14 > 0:58:18we just have to stay one step ahead.
0:58:18 > 0:58:21We don't have to totally win, that's not the goal.
0:58:21 > 0:58:26The goal is simply to find out enough to be able to do something useful
0:58:26 > 0:58:29and then let the next scientist find out the next thing that's enough
0:58:29 > 0:58:31to do something useful.
0:58:43 > 0:58:46Subtitles by Red Bee Media Ltd