0:00:02 > 0:00:05We're discovering astonishing things about the human body
0:00:05 > 0:00:09all the time, through people who are different from most.
0:00:11 > 0:00:12I'm Gabriel Weston.
0:00:12 > 0:00:15As a surgeon, I've spent years studying the human body
0:00:15 > 0:00:20and the secrets of how it works are often revealed
0:00:20 > 0:00:24by the most rare and surprising of cases.
0:00:25 > 0:00:29So, I've searched the world to find these extraordinary people
0:00:29 > 0:00:31and bring you their stories.
0:00:31 > 0:00:34This is my heart.
0:00:34 > 0:00:36I'm the only one that has this.
0:00:36 > 0:00:39I'm Jordy Cernik and I can't feel fear.
0:00:39 > 0:00:43My name is Harnaam Kaur and I'm a fabulous bearded lady.
0:00:43 > 0:00:46With the help of the doctors that treat them,
0:00:46 > 0:00:49and some of the world's leading scientists,
0:00:49 > 0:00:54I'll be uncovering exactly what makes their bodies unique.
0:00:55 > 0:00:58I'm going to show you the hidden processes
0:00:58 > 0:01:00that make them exceptional.
0:01:02 > 0:01:03Just look at that!
0:01:05 > 0:01:09I'll discover how they're leading us to the cures of the future.
0:01:09 > 0:01:14When we make a breakthrough like this, it is very exciting.
0:01:14 > 0:01:17And I'll use the latest technology
0:01:17 > 0:01:20to uncover the secrets of their bodies
0:01:20 > 0:01:25and reveal how all of these cases are giving us a new understanding
0:01:25 > 0:01:31of the most amazing natural machine on the planet - the human body.
0:01:42 > 0:01:46'The human body is a wonder of the natural world -
0:01:46 > 0:01:50'a beautifully crafted piece of precision engineering
0:01:50 > 0:01:55'with thousands of intricate parts working in perfect harmony.'
0:01:55 > 0:01:58It's only when we test a machine to its limits
0:01:58 > 0:02:00that we know what it's capable of.
0:02:01 > 0:02:06In this programme, we're going to delve into the secret inner workings
0:02:06 > 0:02:10of the human body through some truly extraordinary cases.
0:02:10 > 0:02:15We'll discover why this woman had two hearts,
0:02:15 > 0:02:20why this woman's body can bend in ways no-one else's can
0:02:20 > 0:02:25and how this man can produce sounds that seem impossible.
0:02:26 > 0:02:28Through these cases,
0:02:28 > 0:02:32I'm going to reveal a hidden world of astonishing mechanics,
0:02:32 > 0:02:35materials and intricate working parts,
0:02:35 > 0:02:39unsurpassed by anything we humans have invented.
0:02:40 > 0:02:45And our first few cases are people with some surprising variations
0:02:45 > 0:02:47to the fundamental human model,
0:02:47 > 0:02:51who can perform feats that seem almost superhuman.
0:02:53 > 0:02:57MUSIC: Born To Run by Bruce Springsteen
0:03:03 > 0:03:06One time, I signed up for a 200 mile, 12-person relay race,
0:03:06 > 0:03:08just to do it solo.
0:03:12 > 0:03:16I actually ran 50 marathons in all 50 of the United States
0:03:16 > 0:03:19in 50 consecutive days.
0:03:22 > 0:03:24My name is Dean Karnazes
0:03:24 > 0:03:28and I've run through three days and three nights without stopping.
0:03:29 > 0:03:33# Baby, we were born to run. #
0:03:35 > 0:03:38The night of my 30th birthday, and I'm in a bar
0:03:38 > 0:03:41and I'm doing what we do, here in America, on our 30th birthdays.
0:03:41 > 0:03:43I was drinking with my buddies.
0:03:44 > 0:03:47I had a really comfortable, cush job in San Francisco
0:03:47 > 0:03:49as a young corporate executive.
0:03:49 > 0:03:53I had all the perks you would imagine - a company car,
0:03:53 > 0:03:58stock options, health insurance - but I was miserable.
0:03:58 > 0:04:01And I just had this epiphany - leave the bar.
0:04:01 > 0:04:04And at 11 o'clock at night, drunk,
0:04:04 > 0:04:07and ran 30 miles, straight through the night that night.
0:04:11 > 0:04:14I remember, when I ran, that was the only time I really felt alive
0:04:14 > 0:04:17and when I felt most alive is when I was struggling
0:04:17 > 0:04:20and in great pain and trying to persist.
0:04:20 > 0:04:24And something almost primordial bubbled up that night.
0:04:27 > 0:04:29That was 24 years ago
0:04:29 > 0:04:33and you could say that Dean hasn't stopped running since.
0:04:33 > 0:04:38He's completed some of the toughest endurance events on the planet,
0:04:38 > 0:04:40from the South Pole to the Silk Road.
0:04:41 > 0:04:45He's the ultimate ultra-marathon man.
0:04:47 > 0:04:50So, some of the races I've run have been 50 miles,
0:04:50 > 0:04:53100 miles, 200 miles.
0:04:55 > 0:05:00Dean decided to test how far he could run without stopping.
0:05:01 > 0:05:04And after actually making it 350 miles
0:05:04 > 0:05:07in over 81 hours of continuous running,
0:05:07 > 0:05:09I think I found my limit.
0:05:09 > 0:05:12Cos that third night without sleep was really vexing.
0:05:12 > 0:05:15I got through the first two nights with no sleep OK,
0:05:15 > 0:05:17but that third night, I was hallucinating,
0:05:17 > 0:05:19I was falling asleep as I was running
0:05:19 > 0:05:22and I thought, "This is kind of the functional limit
0:05:22 > 0:05:24"that a human can go, at least myself."
0:05:26 > 0:05:30So, if it weren't for the minor inconvenience of having to sleep,
0:05:30 > 0:05:34Dean could just keep running, apparently without needing to stop.
0:05:34 > 0:05:38Here is a man who seems to completely redefine what it means
0:05:38 > 0:05:43to push your body to the limits, but how is this humanly possible?
0:05:47 > 0:05:49My name is Anthony Luke
0:05:49 > 0:05:52and I'm the Director of Primary Care Sports Medicine,
0:05:52 > 0:05:54here at the University of California in San Francisco.
0:05:54 > 0:05:59For Dean, I think he's the epitome of the ultra-marathon athlete.
0:05:59 > 0:06:01I don't think I've heard of anyone
0:06:01 > 0:06:04put as many miles on his body as he has.
0:06:10 > 0:06:14To try to get to the bottom of Dean's extraordinary abilities,
0:06:14 > 0:06:18Dr Luke and his colleague, exercise physiologist Dr Nicole Pinto,
0:06:18 > 0:06:20have invited him to their lab.
0:06:20 > 0:06:22Put your heart rate monitor on.
0:06:24 > 0:06:27The team are looking at two indicators of Dean's fitness.
0:06:29 > 0:06:33The first is how efficiently his body uses oxygen.
0:06:36 > 0:06:38Dean's doing really well so far.
0:06:38 > 0:06:41We have him at some lower stages and as we ramp him up,
0:06:41 > 0:06:43he'll probably get more tired.
0:06:44 > 0:06:48Are you ready for the next stage, Dean? Move him up to 7.7.
0:06:48 > 0:06:53As well as analysing his oxygen use, they're also testing the levels
0:06:53 > 0:06:56of a chemical in his blood called lactate.
0:06:56 > 0:06:57Are you doing OK?
0:06:57 > 0:07:01When we're exercising, there are all these processes occurring
0:07:01 > 0:07:04where we're metabolising or breaking down nutrients
0:07:04 > 0:07:07and those processes have by-products.
0:07:07 > 0:07:10Lactate is a by-product of exercise.
0:07:10 > 0:07:13It's a substance which is built up in the muscles
0:07:13 > 0:07:16and when it reaches a certain point,
0:07:16 > 0:07:20it has to be cleared from the muscles into the blood.
0:07:20 > 0:07:22I sort of think of lactate as being the thing
0:07:22 > 0:07:26that causes that burn when you do exercise.
0:07:26 > 0:07:29Are you ready for the next stage, Dean? Give me a thumbs-up. Good.
0:07:29 > 0:07:30And we're going up.
0:07:30 > 0:07:33Anthony and Nicole take regular blood tests
0:07:33 > 0:07:36to measure Dean's lactate levels.
0:07:36 > 0:07:38- 17, very hard.- OK.- Going up.
0:07:38 > 0:07:42- Let me know when, Nicole. - And go ahead.
0:07:42 > 0:07:43Are you OK, Dean?
0:07:43 > 0:07:48The team are also taking a detailed look at the way that Dean runs.
0:07:48 > 0:07:52Place markers here on your lower back and upper back.
0:07:52 > 0:07:58We're testing Dean's biomechanics by using a 3-D marker system.
0:08:00 > 0:08:02As they analyse the results,
0:08:02 > 0:08:07the team hope to find the secret of Dean's extraordinary ability.
0:08:10 > 0:08:13- These are the results? - Yeah, how are you feeling now?
0:08:13 > 0:08:16- Rested a little bit? - I've recovered now, yeah.- OK.
0:08:16 > 0:08:18So, first we're going to look at heart rate
0:08:18 > 0:08:21- and we're going to do that in comparison to speed.- Mm-hmm.
0:08:21 > 0:08:24So, if you look here at the blue line, that's your heart rate
0:08:24 > 0:08:27and we see a nice smooth increase, which is expected
0:08:27 > 0:08:29for an ultra-endurance athlete.
0:08:31 > 0:08:33Dean is at peak fitness.
0:08:34 > 0:08:36But this alone doesn't explain
0:08:36 > 0:08:39why he can run such superhuman distances.
0:08:42 > 0:08:45So, now the team analyse his technique.
0:08:47 > 0:08:50This is just a visual 3-D reconstruction
0:08:50 > 0:08:53of your skeleton actually running.
0:08:53 > 0:08:55You do kind of flex at the knee
0:08:55 > 0:08:57- a little bit more than someone else. - I see that, yeah.
0:08:57 > 0:09:01That'll have some advantages when you're kind of absorbing shock,
0:09:01 > 0:09:05as well as your efficiency to kind of push yourself back.
0:09:07 > 0:09:11Dean's efficient technique will help keep him going
0:09:11 > 0:09:15but it can't explain why his muscles don't eventually tire.
0:09:17 > 0:09:19The scientists hope they might find a clue
0:09:19 > 0:09:22in the final results from the lactate test.
0:09:23 > 0:09:26Most of us hit a point where our muscles start to burn.
0:09:26 > 0:09:29This is known as our lactate threshold,
0:09:29 > 0:09:33when lactate is being produced faster than we can get rid of it.
0:09:33 > 0:09:36But the results suggest Dean is different.
0:09:38 > 0:09:40You're starting at a nice low level.
0:09:40 > 0:09:44You start exercising and, actually, your blood lactate level dips
0:09:44 > 0:09:47and that's probably because your heart rate's kind of going,
0:09:47 > 0:09:51it's moving blood and your body's very efficient at clearing that.
0:09:51 > 0:09:56You're holding a nice low blood lactate level at your sweet spot.
0:09:56 > 0:09:58- Yeah.- Where you like running,
0:09:58 > 0:10:01where you run all those hundreds of miles, you're very economical.
0:10:04 > 0:10:08So, this is the secret of Dean's amazing abilities.
0:10:08 > 0:10:12His blood is able to quickly clear lactate from his muscles
0:10:12 > 0:10:17which, in most of us, would make it too painful to carry on.
0:10:17 > 0:10:20People always ask me, "How long are you going to keep this up?"
0:10:20 > 0:10:23I always tell people, "My finish line is a pine box."
0:10:24 > 0:10:29By around 50, we see people slowing down a little bit,
0:10:29 > 0:10:32people may be getting a little more aches and pains or even problems.
0:10:32 > 0:10:35Certainly, for Dean, he's continued to do these things
0:10:35 > 0:10:38for the last ten years, at least that I've known him.
0:10:38 > 0:10:40I don't see any signs of slowing down.
0:10:42 > 0:10:44I still love to run as much as I did
0:10:44 > 0:10:47and if I wake up one morning and that passion and that fire's gone,
0:10:47 > 0:10:50I'll stop running, but right now, it's still white hot.
0:10:50 > 0:10:52So, I just love exploring the limits
0:10:52 > 0:10:54and I think I'm going to keep doing it as long as I can.
0:10:59 > 0:11:03What enables Dean to power through these incredible feats of endurance
0:11:03 > 0:11:06are these - his skeletal muscles.
0:11:06 > 0:11:09And, in fact, it takes about 200 of these muscles
0:11:09 > 0:11:11just to take one single step.
0:11:13 > 0:11:17All over our bodies, even where you wouldn't expect them,
0:11:17 > 0:11:18there are muscles at work,
0:11:18 > 0:11:23keeping every part of our machinery moving and functioning.
0:11:23 > 0:11:26Now, I trained as an ear, nose and throat doctor
0:11:26 > 0:11:29and I spent a lot of my time focussed on a group of muscles
0:11:29 > 0:11:32that most people have probably never heard of.
0:11:32 > 0:11:36These are the muscles of the larynx or voice box.
0:11:36 > 0:11:37Together with our tongue,
0:11:37 > 0:11:42these muscles work collectively to do something almost magical.
0:11:42 > 0:11:46They produce the very precise set of vibrations in the air
0:11:46 > 0:11:49that give each of us our unique voice.
0:11:51 > 0:11:54But the next extraordinary person we're about to meet
0:11:54 > 0:11:58can use this machinery to make sounds that should be impossible.
0:12:01 > 0:12:04HE SINGS TWO NOTES SIMULTANEOUSLY
0:12:04 > 0:12:10This man is a professional singer. But he has no ordinary voice.
0:12:10 > 0:12:14HE SINGS ODE TO JOY WITH TWO SIMULTANEOUS RUNS OF NOTES
0:12:20 > 0:12:24My name is Wolfgang Saus and I can sing two notes at the same time.
0:12:24 > 0:12:27This mysterious style of singing
0:12:27 > 0:12:30is known as polyphonic or overtone singing.
0:12:32 > 0:12:35Most of us can make only one note at a time,
0:12:35 > 0:12:38so how is it possible to produce two?
0:12:41 > 0:12:45Over 30 years ago, Wolfgang set out to answer that very question.
0:12:45 > 0:12:49Back then, he was a successful research chemist,
0:12:49 > 0:12:51for whom singing was a hobby.
0:12:51 > 0:12:53One day, he opened his mouth
0:12:53 > 0:12:56and what came out astonished him.
0:12:56 > 0:12:59HE SINGS TWO SIMULTANEOUS RUNS OF NOTES
0:12:59 > 0:13:01I was amazed about the sound
0:13:01 > 0:13:08and to hear a full orchestra in your own voice is absolutely amazing.
0:13:09 > 0:13:11But he had absolutely no idea
0:13:11 > 0:13:15how he was producing these extraordinary sounds.
0:13:15 > 0:13:20So, I went home and tried many things.
0:13:20 > 0:13:22HE MAKES TRILLING SOUND
0:13:23 > 0:13:27I first to the mirror and looked into my throat,
0:13:27 > 0:13:31but this was a stupid idea. I didn't know how my voice worked.
0:13:32 > 0:13:36I tried something with my tongue and suddenly there was an overtone
0:13:36 > 0:13:40and then it was lost again and then I couldn't find it.
0:13:40 > 0:13:43HE TRILLS
0:13:44 > 0:13:46'Wolfgang gave up his research job
0:13:46 > 0:13:51'and decided to turn his unusual singing talent into a new career,
0:13:51 > 0:13:54'and to perfect his technique,'
0:13:54 > 0:13:56he wanted to uncover the secret
0:13:56 > 0:14:00of exactly how he was making these astonishing sounds.
0:14:00 > 0:14:03'I think I'm a scientist'
0:14:03 > 0:14:06and I want to know how things work.
0:14:08 > 0:14:12And there was one man who could help him unlock that mystery.
0:14:13 > 0:14:16Professor Bernhard Richter is the head
0:14:16 > 0:14:18of the Freiburg Institute for Musicians' Medicine.
0:14:18 > 0:14:22He's a trained opera singer and a doctor.
0:14:25 > 0:14:26Open your mouth, please.
0:14:28 > 0:14:32Science is art and art is science, for me,
0:14:32 > 0:14:35so I try to help singers understand
0:14:35 > 0:14:38what's going on inside their bodies.
0:14:38 > 0:14:43And Professor Richter has a few state-of-the-art tools to help him.
0:14:43 > 0:14:45WOLFGANG SINGS A SINGLE NOTE
0:14:45 > 0:14:47This software analyses sound
0:14:47 > 0:14:50and helps visualise the notes being produced.
0:14:50 > 0:14:54Please make just a normal sound of a normal singer,
0:14:54 > 0:14:56opera-like singer, you know.
0:14:56 > 0:14:58WOLFGANG SINGS A SINGLE NOTE
0:14:58 > 0:15:01When we sing normally, we produce
0:15:01 > 0:15:03lots of different frequencies at once,
0:15:03 > 0:15:05shown by the different bars here.
0:15:06 > 0:15:09Our brain combines these different frequencies
0:15:09 > 0:15:12and we hear a single note.
0:15:12 > 0:15:15Now, can you please do, for me, the overtone singing?
0:15:15 > 0:15:19WOLFGANG SINGS WITH OVERTONES
0:15:24 > 0:15:26But Wolfgang is able to make us think
0:15:26 > 0:15:29he's singing two notes at the same time.
0:15:29 > 0:15:35He does this by filtering out some overtones and making others louder.
0:15:37 > 0:15:42What you heard was all the time the same fundamental frequency,
0:15:42 > 0:15:46but we heard the changing of the overtones.
0:15:46 > 0:15:50RECORDING OF WOLFGANG SINGING WITH OVERTONES
0:15:54 > 0:15:56To work out how Wolfgang is able to do this,
0:15:56 > 0:16:01Professor Richter put him into an MRI scanner and made him sing.
0:16:04 > 0:16:08First, he's looking at what happens when Wolfgang sings normally.
0:16:10 > 0:16:14Now, the most important thing is the shape of the tongue.
0:16:14 > 0:16:18You can see that the tongue is quite flat here
0:16:18 > 0:16:20and there is a narrowing
0:16:20 > 0:16:24between the back of the tongue and the pharynx wall here.
0:16:24 > 0:16:27When Wolfgang sings normally,
0:16:27 > 0:16:30his tongue creates a single resonance chamber.
0:16:30 > 0:16:33This is the black area on the scan,
0:16:33 > 0:16:37essentially a chamber full of air where sound waves resonate -
0:16:37 > 0:16:40in this case, producing a single sound.
0:16:41 > 0:16:44But when he switches to overtone singing,
0:16:44 > 0:16:47Wolfgang does something completely different.
0:16:47 > 0:16:50RECORDING OF WOLFGANG SINGING WITH OVERTONES
0:16:50 > 0:16:54You can see clearly how the tip of his tongue is going upwards
0:16:54 > 0:16:59and creating this chamber underneath the tongue.
0:16:59 > 0:17:05The black column there is the air and the more grey are the muscle.
0:17:05 > 0:17:07And you can see, for the different overtones,
0:17:07 > 0:17:10he has a different tongue shape here.
0:17:10 > 0:17:15Very impressive how much he can move, actually, his tongue.
0:17:17 > 0:17:21So, his tongue is creating two different resonance chambers
0:17:21 > 0:17:24and that has a profound effect on what we hear.
0:17:26 > 0:17:28There's a completely different vocal sound
0:17:28 > 0:17:32and this is what you perceive. You perceive two tones.
0:17:32 > 0:17:35Actually, I'm still singing the same as before,
0:17:35 > 0:17:37but the brain makes two tones out of it.
0:17:37 > 0:17:40HE SINGS WITH OVERTONES
0:17:40 > 0:17:44This is the secret to singing two notes at the same time.
0:17:44 > 0:17:47Wolfgang alters the shape of his mouth
0:17:47 > 0:17:50to amplify particular frequencies.
0:17:52 > 0:17:55In theory, it's something that anyone could do,
0:17:55 > 0:17:58but it takes years of dedicated practice.
0:17:58 > 0:18:02It's fantastic to see, after many years of singing
0:18:02 > 0:18:06and investigating and trying to find out
0:18:06 > 0:18:08what happens in overtone singing,
0:18:08 > 0:18:11to, in the end, see what the tongue does and it's...
0:18:11 > 0:18:15- It's not imagination. It's more reality, you know.- Yeah.
0:18:18 > 0:18:23Wolfgang's rare skill reveals how we can consciously manipulate
0:18:23 > 0:18:27our muscles to achieve extraordinary things.
0:18:29 > 0:18:33Our bodies are full of moving parts that are working all the time.
0:18:36 > 0:18:38And it's often when something goes wrong
0:18:38 > 0:18:41that we see what they're really capable of,
0:18:41 > 0:18:44as we'll discover in our next few cases.
0:18:44 > 0:18:46Take the heart, for example.
0:18:46 > 0:18:51In a single day and 100,000 beats,
0:18:51 > 0:18:55this heart can pump 2,000 gallons of oxygen-rich blood
0:18:55 > 0:18:58around 60,000 miles of vessels.
0:19:00 > 0:19:03'And in one of the most astonishing cases I've come across,
0:19:03 > 0:19:06'a life-threatening problem with one girl's heart
0:19:06 > 0:19:11'has changed our understanding of this most vital organ.'
0:19:16 > 0:19:18The fact that this young woman is alive
0:19:18 > 0:19:21is one of the most dramatic successes
0:19:21 > 0:19:23in recent medical history.
0:19:26 > 0:19:29My name is Hannah Clark and I used to have two hearts.
0:19:31 > 0:19:34Soon after Hannah was born, her parents, Liz and Paul,
0:19:34 > 0:19:37began to worry that something might be wrong.
0:19:39 > 0:19:42It was definitely the screaming. It was piercing.
0:19:42 > 0:19:45There was never a time that she was a well baby.
0:19:47 > 0:19:49A chest X-ray when she was eight months old
0:19:49 > 0:19:52revealed Hannah had an enlarged heart,
0:19:52 > 0:19:55a condition called dilated cardiomyopathy.
0:19:55 > 0:19:57BABY CRIES
0:19:57 > 0:20:02As a result, her heart struggled to pump blood around her body.
0:20:04 > 0:20:07Every time you would think it was not so bad,
0:20:07 > 0:20:09and then something else would happen,
0:20:09 > 0:20:11and then it would get worse and worse.
0:20:13 > 0:20:17Liz and Paul were told Hannah would need a heart transplant.
0:20:21 > 0:20:25Consultant cardiologist Dr Dirk Wilson first met Hannah
0:20:25 > 0:20:27when she was only eight months old.
0:20:29 > 0:20:34She weighed less than 10kg and the likelihood of finding a donor heart
0:20:34 > 0:20:37for an infant of that size is actually quite small.
0:20:39 > 0:20:42Without a heart exactly the right size for Hannah,
0:20:42 > 0:20:44the doctors decided to try
0:20:44 > 0:20:47a different and unusual kind of transplant.
0:20:50 > 0:20:53It's called a heterotopic or piggyback transplant.
0:20:54 > 0:20:59Instead of removing Hannah's heart, the doctors would leave it in place
0:20:59 > 0:21:01and implant a second one from a donor.
0:21:03 > 0:21:06The idea was that both hearts would then work together
0:21:06 > 0:21:09to pump blood around her body.
0:21:12 > 0:21:16Hannah was just two years old when she had her piggyback transplant.
0:21:17 > 0:21:21They told us if she didn't have the transplant when she did,
0:21:21 > 0:21:23she wouldn't have made it. She was that ill.
0:21:25 > 0:21:27But the operation was a success.
0:21:28 > 0:21:31Her two hearts beating together worked better
0:21:31 > 0:21:34than anyone could have imagined.
0:21:35 > 0:21:40But when Hannah was six, she found herself back in hospital.
0:21:40 > 0:21:43She went ill one day and these glands started to pop up,
0:21:43 > 0:21:46- didn't they?- Her kidneys started failing. She was really ill.
0:21:49 > 0:21:50As with any transplant,
0:21:50 > 0:21:54there was a risk that Hannah's body would reject her new heart,
0:21:54 > 0:21:58that her immune system would see it as something foreign
0:21:58 > 0:22:00and her body would attack it.
0:22:00 > 0:22:02So, for this reason, ever since her transplant,
0:22:02 > 0:22:06she'd been taking drugs to suppress her immune system.
0:22:06 > 0:22:09But these had left her vulnerable to illness
0:22:09 > 0:22:13and she'd developed life-threatening complications.
0:22:15 > 0:22:18They called us in the room and they said, um...
0:22:20 > 0:22:22.."We think she's only got 12 hours to live."
0:22:27 > 0:22:29Hannah received lifesaving treatment
0:22:29 > 0:22:33and her doctors reduced her dose of anti-immunity drugs.
0:22:35 > 0:22:38Her immune system began to recover
0:22:38 > 0:22:41but that had a devastating side effect.
0:22:43 > 0:22:45By reducing the anti-immunity drugs,
0:22:45 > 0:22:49it meant that the heart was being rejected
0:22:49 > 0:22:52and its function had gone down - the donor heart.
0:22:53 > 0:22:57Slowly, over time, the donor heart that had kept Hannah alive
0:22:57 > 0:23:00was being attacked by her own body...
0:23:01 > 0:23:04..a situation that could be fatal.
0:23:06 > 0:23:10But then, doctors noticed something remarkable.
0:23:10 > 0:23:14Hannah's own heart now appeared to be recovering...
0:23:15 > 0:23:19..something they'd never seen a damaged heart do before.
0:23:20 > 0:23:23And it gave them a radical idea.
0:23:24 > 0:23:28We started to wonder, perhaps if they took out the donor heart,
0:23:28 > 0:23:29wouldn't that be the way forward?
0:23:29 > 0:23:32Would it be the right thing to remove the donor heart
0:23:32 > 0:23:35and would that actually improve Hannah's situation?
0:23:35 > 0:23:41The doctors decided to go ahead with this groundbreaking operation.
0:23:41 > 0:23:45In February, 2006, they removed the donor heart,
0:23:45 > 0:23:50leaving Hannah's own heart to function without any assistance.
0:23:50 > 0:23:55It was a world first and nobody could predict the outcome.
0:24:00 > 0:24:02- TV NEWS REPORT:- A hug from her mum,
0:24:02 > 0:24:05as Hannah Clark is overcome by emotion at a press conference.
0:24:05 > 0:24:10The heart is not showing any signs of deterioration.
0:24:10 > 0:24:13As a matter of fact, it's getting better and better.
0:24:14 > 0:24:18After just five days in hospital, Hannah returned home.
0:24:18 > 0:24:22I didn't expect how she came out of it so quick.
0:24:22 > 0:24:24It was just lovely to see,
0:24:24 > 0:24:26cos we didn't think that was going to happen.
0:24:29 > 0:24:32Hannah has been on a remarkable medical journey,
0:24:32 > 0:24:34one that's changed the way
0:24:34 > 0:24:37doctors approach life-threatening heart problems.
0:24:40 > 0:24:43If there's a chance a diseased heart might recover if rested,
0:24:43 > 0:24:47as happened with Hannah, doctors are now less likely
0:24:47 > 0:24:50to perform a transplant as a first option.
0:24:50 > 0:24:53Instead, they may try a robotic device
0:24:53 > 0:24:56to assist the heart and give it a chance to recover.
0:24:58 > 0:25:02Hannah's case has shown us that even in situations where we think
0:25:02 > 0:25:05there is no hope of recovery, recovery can occur.
0:25:08 > 0:25:12Hannah is now 23 and has a baby of her own.
0:25:12 > 0:25:14I always think about the doctors and the surgeons
0:25:14 > 0:25:18who done my operations and stuff, really.
0:25:18 > 0:25:20I wouldn't really be here without them.
0:25:20 > 0:25:24They practically brought me back to life not just once - twice, really.
0:25:24 > 0:25:27I'm really proud and really glad I had the doctors I had.
0:25:31 > 0:25:35'As a surgeon, I can't help but be excited by cases like Hannah's,
0:25:35 > 0:25:38'where a life-threatening medical problem is solved
0:25:38 > 0:25:41'by pioneering surgery.
0:25:41 > 0:25:46'But sometimes, things go wrong in our bodies that don't need fixing.
0:25:46 > 0:25:50'Occasionally a fault can even give us an edge.'
0:25:50 > 0:25:52In our next case,
0:25:52 > 0:25:56a flaw in the finely-tuned machinery of her body,
0:25:56 > 0:25:59has given one woman the ability to move in ways
0:25:59 > 0:26:03that, for the rest of us, are completely impossible.
0:26:10 > 0:26:14My name is Claudia Hughes and I can bend in ways that no-one else can.
0:26:15 > 0:26:19Like lots of children, Claudia loved dance and gymnastics,
0:26:19 > 0:26:24but people around her noticed that she was no ordinary dancer.
0:26:24 > 0:26:26Claudia was different.
0:26:27 > 0:26:30I remember getting a ballet book from my mum
0:26:30 > 0:26:33and there was, like, a picture of a girl doing splits in there
0:26:33 > 0:26:36and I was, like, "That's so cool. I'm going to try that."
0:26:36 > 0:26:38I could just do the splits straightaway.
0:26:39 > 0:26:43Claudia found that she was naturally bendier than most people.
0:26:44 > 0:26:47We used to have to do stretches at the beginning of a dance class
0:26:47 > 0:26:49and we had to do this one exercise
0:26:49 > 0:26:52where we were just kicking our leg up behind us.
0:26:52 > 0:26:54And my leg just went all the way round
0:26:54 > 0:26:56and gave me this massive black eye.
0:26:59 > 0:27:02Claudia now performs professionally.
0:27:02 > 0:27:06I'm a full-time contortionist. This is my career.
0:27:06 > 0:27:08I'm the only British contortionist
0:27:08 > 0:27:11to be able to do the spinning Marinelli bend.
0:27:11 > 0:27:15Recently, I've been proclaimed Britain's bendiest woman,
0:27:15 > 0:27:17which is quite an achievement.
0:27:20 > 0:27:25When you see Claudia in action, it's completely mind-boggling
0:27:25 > 0:27:29and the obvious question is, how on Earth can she do it?
0:27:29 > 0:27:34What is it about her body that enables her to bend in ways
0:27:34 > 0:27:36that would be impossible for most of us?
0:27:38 > 0:27:41Dr Emma Redding is Head of Dance Science
0:27:41 > 0:27:46at the Trinity Laban Conservatoire of Music and Dance.
0:27:46 > 0:27:48I'm really interested in hypermobility.
0:27:48 > 0:27:51That's different to flexibility.
0:27:51 > 0:27:55Flexibility refers to the range of motion at a joint,
0:27:55 > 0:27:59and dancers, for example, and gymnasts have good flexibility.
0:28:00 > 0:28:02But hypermobility is something different.
0:28:02 > 0:28:07That's when a joint goes beyond its sort of extension, its normal range.
0:28:09 > 0:28:13Dr Redding has invited Claudia to her lab
0:28:13 > 0:28:16to try to get to the bottom of her extraordinary abilities.
0:28:16 > 0:28:20She uses a device called a goniometer
0:28:20 > 0:28:24to discover just how hypermobile Claudia really is.
0:28:24 > 0:28:26- Is that good?- Yeah.- OK, great.
0:28:26 > 0:28:28Interestingly, the elbows -
0:28:28 > 0:28:31- you could extend those 17 degrees beyond normal.- Mm.
0:28:31 > 0:28:35And your knees, 17, 18 degrees beyond a normal person's.
0:28:37 > 0:28:42Claudia's range of movement goes far beyond the normal limits.
0:28:42 > 0:28:44It's greater than in anyone Emma has seen before,
0:28:44 > 0:28:48including highly trained and flexible dancers.
0:28:50 > 0:28:53And Dr Redding knows the likely cause.
0:28:55 > 0:28:57Essentially, if you've been born with hypermobility,
0:28:57 > 0:28:59then it probably means that the connective tissues
0:28:59 > 0:29:02that surround those joints are lax.
0:29:02 > 0:29:05They're looser than normal joints.
0:29:07 > 0:29:09Claudia is far bendier than most of us
0:29:09 > 0:29:12because there's something wrong with her ligaments
0:29:12 > 0:29:14which hold her joints together.
0:29:14 > 0:29:17They're made from a material called collagen.
0:29:17 > 0:29:21But in Claudia, it's weaker than it should be.
0:29:21 > 0:29:27This is what gives her superhuman abilities, but they come at a price.
0:29:27 > 0:29:31Individuals with hypermobile joints have to work harder
0:29:31 > 0:29:33- to stabilise those joints.- Yeah.
0:29:33 > 0:29:36There's more muscle tension created during the day
0:29:36 > 0:29:41- to sort of maintain that stability. - I do get tired really easily.
0:29:41 > 0:29:44In a sense, you've been expending more energy during the day
0:29:44 > 0:29:46than a normal person.
0:29:46 > 0:29:50And being so bendy also carries a risk.
0:29:50 > 0:29:54Hypermobile joints can twist very easily
0:29:54 > 0:29:57and often can suffer from injury.
0:29:59 > 0:30:03With weak ligaments, Claudia is at risk of hurting herself
0:30:03 > 0:30:06but, remarkably, she rarely gets injured.
0:30:08 > 0:30:12To find out why this might be, Dr Redding carries out another test.
0:30:13 > 0:30:16- I'm just going to take a quick measurement.- OK.
0:30:16 > 0:30:17Keep your arm there for me.
0:30:18 > 0:30:22And then you try and match the angle with the other arm.
0:30:22 > 0:30:25She's measuring Claudia's awareness
0:30:25 > 0:30:28of the position of her body in space,
0:30:28 > 0:30:31an ability called proprioception.
0:30:31 > 0:30:34So, when we positioned your arm in a particular place,
0:30:34 > 0:30:36we asked you to close your eyes
0:30:36 > 0:30:38and replicate that joint on the other side.
0:30:38 > 0:30:42- Yeah, I found that quite easy.- And you replicated that angle very well.
0:30:42 > 0:30:46So, it does seem that you have good proprioception in your upper body.
0:30:46 > 0:30:49Your brain is registering that it's OK for your body
0:30:49 > 0:30:52to be going to those extreme ranges of motion
0:30:52 > 0:30:54cos it can sense where they are.
0:30:54 > 0:30:56Right, OK.
0:30:59 > 0:31:03Claudia's awareness of her body helps her to stay in control
0:31:03 > 0:31:08of her bendy joints and so push her body to its absolute limits.
0:31:08 > 0:31:12I love trying new contortion stuff around the house,
0:31:12 > 0:31:15partly because I'm training
0:31:15 > 0:31:17and doing household work at the same time.
0:31:17 > 0:31:21Sometimes, if I have friends over, it's always a bit of a party trick
0:31:21 > 0:31:25to, like, come out of a cupboard or something and scare them.
0:31:26 > 0:31:28I'm just having a great time at the moment.
0:31:28 > 0:31:31I just want to do it for as long as my body can
0:31:31 > 0:31:33and then I'll see what happens.
0:31:38 > 0:31:42Claudia's extraordinary ability to bend her body
0:31:42 > 0:31:46is only physically possible because of an abnormality
0:31:46 > 0:31:49in one of the most prevalent and important materials
0:31:49 > 0:31:52in the human body - collagen.
0:31:53 > 0:31:57And I can show you some of its special properties with this egg.
0:31:57 > 0:32:00But first of all, I need to get rid of its hard shell,
0:32:00 > 0:32:04so I'm just going to put this into a bowl of vinegar, which is an acid.
0:32:04 > 0:32:09If I leave it there for long enough, what I'll end up with is this -
0:32:09 > 0:32:14this amazing thin membrane, which is made of collagen
0:32:14 > 0:32:18and which actually gives the egg its perfect shape,
0:32:18 > 0:32:21since it's the shell that just grows on top of this.
0:32:21 > 0:32:26But the collagen isn't just making the egg look smooth and beautiful,
0:32:26 > 0:32:29it can also do something else which is really cool.
0:32:30 > 0:32:34It's the combination of strength and flexibility in the collagen
0:32:34 > 0:32:37that allows the egg to bounce up and down like that.
0:32:39 > 0:32:43What I'm going to do now is dissect this collagen membrane
0:32:43 > 0:32:47and empty it out, and the contents are spilling out into this bowl.
0:32:48 > 0:32:54And what this leaves me with is this amazing collagen-rich membrane
0:32:54 > 0:32:58round the outside, which is kind of very, very strong,
0:32:58 > 0:33:01but also stretchy and tough.
0:33:02 > 0:33:07It's these properties that make it perfect for stabilising our joints
0:33:07 > 0:33:09and controlling their range of movement.
0:33:09 > 0:33:15But they also play a key role in another part of our body - our skin.
0:33:17 > 0:33:19And there's one fascinating case I've come across
0:33:19 > 0:33:22that's shown me just how important this is.
0:33:22 > 0:33:25It's one of the most moving I've seen.
0:33:30 > 0:33:34For most people, lunch at a cafe with friends is a simple pleasure.
0:33:36 > 0:33:41For Paul, it requires an almost superhuman effort
0:33:41 > 0:33:47because of a condition he's had since birth that affects his skin.
0:33:48 > 0:33:52My name is Paul Martinez and I'm from Stockton, California.
0:33:54 > 0:33:57I have a condition called epidermolysis bullosa.
0:33:57 > 0:33:59They call it EB for short.
0:34:00 > 0:34:03My skin is very fragile, like paper.
0:34:06 > 0:34:11Epidermolysis bullosa, or EB, is a genetic condition
0:34:11 > 0:34:13that makes the skin incredibly delicate.
0:34:13 > 0:34:17Our skin is made up of layers that, in most people,
0:34:17 > 0:34:19are anchored together.
0:34:19 > 0:34:23But in Paul, the layers are only loosely connected,
0:34:23 > 0:34:24so they rub against each other.
0:34:26 > 0:34:30Any small bump can lead to a blister.
0:34:30 > 0:34:34The blister then turns into a second or third-degree burn.
0:34:34 > 0:34:38My skin is always hurting, like it's on fire.
0:34:41 > 0:34:44The hands and feet are particularly vulnerable to damage
0:34:44 > 0:34:48because they're constantly subjected to pressure and friction.
0:34:48 > 0:34:53In Paul's case, his fingers are now encased in scar tissue.
0:34:53 > 0:34:56People with EB are also more likely
0:34:56 > 0:35:00to develop skin cancer as young adults.
0:35:00 > 0:35:04It's a condition for which there's, as yet, no cure.
0:35:04 > 0:35:08Doctors can prescribe drugs to help deal with the constant pain,
0:35:08 > 0:35:11but Paul chooses not to take them.
0:35:13 > 0:35:16I just feel that I value my mind a lot.
0:35:16 > 0:35:20I wasn't blessed in many aspects, but I feel I was blessed in my mind.
0:35:20 > 0:35:23So, I don't want to take that away.
0:35:25 > 0:35:28Paul has refused to let EB hold him back.
0:35:28 > 0:35:31He gained his high school diploma
0:35:31 > 0:35:34and attended the prom just like all the other kids,
0:35:34 > 0:35:36and then later graduated from college
0:35:36 > 0:35:39with a degree in business.
0:35:41 > 0:35:45'Any injury or disease can be risky or painful,
0:35:45 > 0:35:48'but when the problem involves your skin,'
0:35:48 > 0:35:50the material that covers your whole body,
0:35:50 > 0:35:54there isn't a single part of you that isn't affected.
0:35:54 > 0:35:57As a doctor, I find it hard to understand
0:35:57 > 0:36:01how you'd even begin to grapple with a condition like Paul's.
0:36:01 > 0:36:04But he's been working with leading scientists
0:36:04 > 0:36:07who have been uncovering exactly what causes EB
0:36:07 > 0:36:11and he's become one of the very first in the world
0:36:11 > 0:36:14to try out a pioneering new treatment.
0:36:17 > 0:36:22At Stanford University, teams of scientists have spent decades
0:36:22 > 0:36:25trying to decipher the riddle of EB.
0:36:27 > 0:36:33Today, the research is led by dermatologist Dr Peter Marinkovich.
0:36:33 > 0:36:36It's a very terrible existence for these patients,
0:36:36 > 0:36:38to live with pain all their lives
0:36:38 > 0:36:41and then face the prospect of having to have
0:36:41 > 0:36:44this very severe, often fatal, carcinoma
0:36:44 > 0:36:47as they approach their early adulthood.
0:36:49 > 0:36:53The plight of EB sufferers like Paul is a driving force
0:36:53 > 0:36:55for researchers here at Stanford.
0:36:55 > 0:36:59The problem lies in the structure of the skin.
0:37:02 > 0:37:04Skin has different layers.
0:37:04 > 0:37:09The top layer is the epidermis. That's the bit that you can touch.
0:37:09 > 0:37:12Underneath that is the dermis, where new skin cells are formed.
0:37:12 > 0:37:14And in between those two layers,
0:37:14 > 0:37:17there's something called the basement membrane.
0:37:17 > 0:37:19The basement membrane's like a molecular glue.
0:37:19 > 0:37:24You could think of it as links on a chain and there's different proteins
0:37:24 > 0:37:26that make up each of the different links.
0:37:26 > 0:37:28And when any of those links is damaged,
0:37:28 > 0:37:31then the skin will fall apart.
0:37:33 > 0:37:34In Paul's form of EB,
0:37:34 > 0:37:39one of these key proteins is damaged - collagen VII.
0:37:39 > 0:37:42It means the basement membrane doesn't hold
0:37:42 > 0:37:46the layers of Paul's skin together as it should.
0:37:46 > 0:37:49This is why the layers rub against each other,
0:37:49 > 0:37:52causing the pain and blistering he experiences.
0:37:55 > 0:37:58The scientists here at Stanford have discovered that the reason
0:37:58 > 0:38:01for the damage to collagen VII is a faulty gene.
0:38:04 > 0:38:06And this has led to a breakthrough.
0:38:06 > 0:38:10For the first time, there's a potential new treatment for EB,
0:38:10 > 0:38:13by taking some skin cells from the patient,
0:38:13 > 0:38:15correcting the genetic fault,
0:38:15 > 0:38:19and then growing them some new, healthy skin.
0:38:19 > 0:38:22The technique is known as gene therapy.
0:38:24 > 0:38:29A clinical trial is now under way, overseen by specialist Dr Jean Tang.
0:38:31 > 0:38:34We've invested 20 years to develop gene therapy.
0:38:35 > 0:38:38So, patients with EB lack collagen VII.
0:38:38 > 0:38:41They have an abnormal collagen VII gene.
0:38:41 > 0:38:45And in this clinical trial, we take a small biopsy of their skin.
0:38:45 > 0:38:49We grow out the skin cells in a laboratory Petri dish
0:38:49 > 0:38:52and then we use a virus to infect those cells
0:38:52 > 0:38:54with the collagen VII gene.
0:38:56 > 0:38:59Viruses are a standard way, used in gene therapy,
0:38:59 > 0:39:03to carry healthy DNA into human cells,
0:39:03 > 0:39:07because they can penetrate the cell without damaging its structure.
0:39:07 > 0:39:11In this instance, the virus carries a working version of the gene
0:39:11 > 0:39:16for collagen VII into the patient's skin cells in the lab.
0:39:17 > 0:39:20From that, they're producing small skin grafts
0:39:20 > 0:39:23which now have this essential missing protein
0:39:23 > 0:39:24in the basement membrane,
0:39:24 > 0:39:27which is anchoring the epidermis and the dermis together.
0:39:29 > 0:39:32It takes about 30 days to grow up enough cells
0:39:32 > 0:39:34to make about six grafts
0:39:34 > 0:39:38and then we bring the patient back into the operating room,
0:39:38 > 0:39:41give them general anaesthesia
0:39:41 > 0:39:45and now are able to transfer these genetically corrected skin cells
0:39:45 > 0:39:46onto their chronic wounds.
0:39:48 > 0:39:52Over the past three years, the team have treated four patients
0:39:52 > 0:39:55with this groundbreaking therapy, including Paul.
0:39:57 > 0:40:00The patients had chronic wounds that were unhealed for years,
0:40:00 > 0:40:03and now, after the gene-corrected grafts,
0:40:03 > 0:40:07these wounds are closed, they're healed up and the patients,
0:40:07 > 0:40:10in many instances, can now walk on their wounds.
0:40:11 > 0:40:15After the grafting, Paul showed some amazing results.
0:40:15 > 0:40:17He was walking on these areas
0:40:17 > 0:40:20where he'd never walked without pain before
0:40:20 > 0:40:22and he was able to withstand blistering.
0:40:22 > 0:40:26He did amazingly well after the trial.
0:40:28 > 0:40:30'I like to hang out with my friends.
0:40:30 > 0:40:33'We get together and play card games and stuff like that,
0:40:33 > 0:40:38'so it's really fun just to get out and socialise and laugh'
0:40:38 > 0:40:40and have a good time.
0:40:40 > 0:40:44Paul knows that taking part in the trial isn't going to cure him,
0:40:44 > 0:40:46but he has a longer-term goal.
0:40:46 > 0:40:50'I did it for the future of EB.'
0:40:50 > 0:40:52It is a very excruciating disease
0:40:52 > 0:40:54that I don't want anybody to go through,
0:40:54 > 0:40:59so, if I can do my small part and, you know, help find a cure someday,
0:40:59 > 0:41:04then I have no, er, no doubt in just doing it.
0:41:07 > 0:41:12Paul's story, more than any other case, makes me appreciate
0:41:12 > 0:41:15the extraordinary materials that make up our body.
0:41:18 > 0:41:22'But at a deeper level than anything we've seen so far,
0:41:22 > 0:41:26'what keeps the machinery of our body working day and night
0:41:26 > 0:41:30'are hidden systems that operate on the microscopic scale.
0:41:31 > 0:41:35'And our next case involves one of the most important of these -
0:41:35 > 0:41:37'our immune system.'
0:41:39 > 0:41:41It's our body's own in-built
0:41:41 > 0:41:43emergency response and repair system.
0:41:45 > 0:41:47And perhaps the best way to understand
0:41:47 > 0:41:51just what an extraordinary piece of natural engineering it is
0:41:51 > 0:41:56is to see what happens when the system itself goes wrong.
0:41:58 > 0:42:00Right now, you wouldn't know
0:42:00 > 0:42:04that I was dealing with anything out of the ordinary,
0:42:04 > 0:42:10but other days, I look...like a corpse.
0:42:11 > 0:42:16Life for 22-year-old Brynn can be a little unpredictable.
0:42:16 > 0:42:22It's a question of hoping for the best and preparing for the worst.
0:42:22 > 0:42:27Because every day brings a new battle and a new enemy.
0:42:29 > 0:42:31I'm allergic to everything.
0:42:33 > 0:42:38I am allergic to most fruits and vegetables,
0:42:38 > 0:42:43nuts, strong perfumes, cigarette smoke...
0:42:43 > 0:42:45And the list goes on.
0:42:45 > 0:42:50Soy, corn, egg, milk, garlic... She's even allergic to the sun.
0:42:50 > 0:42:55The allergies change every day - or the triggers, I should say.
0:42:55 > 0:42:58Her reactions are so severe, Brynn avoids eating.
0:42:58 > 0:43:02She relies on a feeding tube for her nutrients.
0:43:02 > 0:43:04This is the feeding bag.
0:43:04 > 0:43:07But even this can't protect Brynn.
0:43:07 > 0:43:10This goes into my intestines.
0:43:10 > 0:43:14She's constantly vulnerable to attack and when it happens,
0:43:14 > 0:43:18she doesn't just suffer the odd sneeze or itchy rash.
0:43:18 > 0:43:22She goes into anaphylactic shock.
0:43:22 > 0:43:27Anaphylaxis is a serious life-threatening allergic reaction.
0:43:27 > 0:43:28You can't breathe,
0:43:28 > 0:43:32you feel like your heart's going to either pound out of your chest
0:43:32 > 0:43:33or stop completely.
0:43:33 > 0:43:37If it progresses far enough, then it can lead to death.
0:43:37 > 0:43:41It's a life lottery Brynn's been forced to play since childhood,
0:43:41 > 0:43:45her mystery reactions steadily worsening as she's grown older.
0:43:48 > 0:43:54I went from always active, always on my bike,
0:43:54 > 0:43:56third-degree black belt taekwondo.
0:43:56 > 0:44:00Then that kind of was taken over by the illness.
0:44:00 > 0:44:02A lot of doctors had a hard time
0:44:02 > 0:44:06explaining the symptoms that I suffered.
0:44:06 > 0:44:12It's very obvious that I had something seriously wrong,
0:44:12 > 0:44:14but no-one could explain what it was.
0:44:14 > 0:44:18Having allergic reactions to pretty much everything,
0:44:18 > 0:44:22and with her doctors baffled, it would have been easy for Brynn
0:44:22 > 0:44:26to just give up and accept that her body was never going to work
0:44:26 > 0:44:27the way it should.
0:44:27 > 0:44:31But she and her family were determined to persevere
0:44:31 > 0:44:35and get to the bottom of this mysterious condition.
0:44:38 > 0:44:41The man who would help them is Dr Lawrence Afrin,
0:44:41 > 0:44:43a specialist in blood disorders.
0:44:46 > 0:44:48Brynn's case is actually severe.
0:44:48 > 0:44:54The symptoms she had when I first saw her went well beyond allergies.
0:44:54 > 0:44:58The essence of this disease, actually,
0:44:58 > 0:45:02is much more chronic inflammation.
0:45:02 > 0:45:05Inflammation isn't a bad thing.
0:45:05 > 0:45:09It's our body's way of fighting infection and helping us heal.
0:45:09 > 0:45:11But too much at the wrong time and wrong place
0:45:11 > 0:45:15can have a serious impact on our bodies.
0:45:15 > 0:45:19Something was making Brynn's body overreact.
0:45:19 > 0:45:23And Dr Afrin suspected the attack wasn't coming from the outside
0:45:23 > 0:45:25but from an enemy within -
0:45:25 > 0:45:30a particular type of white blood cell, known as a mast cell.
0:45:31 > 0:45:37Mast cells stand guard, looking out for insults upon the body, assaults.
0:45:37 > 0:45:41And it can be infections, sometimes it's trauma.
0:45:41 > 0:45:46There's no other defence system in the body that reacts as quickly,
0:45:46 > 0:45:49as instantaneously as the mast cell.
0:45:51 > 0:45:54Mast cells are present in nearly all of our tissue.
0:45:54 > 0:45:58They swing into action to defend our body from infection,
0:45:58 > 0:46:02using an array of chemical defences called mediators.
0:46:02 > 0:46:05The most potent is histamine.
0:46:07 > 0:46:09The dominant effect from histamine is itching.
0:46:09 > 0:46:11When we suffer an insect bite,
0:46:11 > 0:46:14we know that there's a local reaction -
0:46:14 > 0:46:17redness and some swelling and some itching.
0:46:17 > 0:46:21Histamine is closely involved in producing that sensation.
0:46:21 > 0:46:24But, unfortunately, sometimes we get the situation
0:46:24 > 0:46:26where the mast cells start misbehaving
0:46:26 > 0:46:30and they start putting out the wrong mediators,
0:46:30 > 0:46:34sometimes when there's not even any trigger at all.
0:46:36 > 0:46:39Brynn's mast cells were pretty dysfunctional.
0:46:39 > 0:46:44It's a condition known as mast cell activation syndrome.
0:46:44 > 0:46:47Brynn's mast cells were releasing too much histamine
0:46:47 > 0:46:51and causing inflammation when it wasn't needed.
0:46:51 > 0:46:54While Dr Afrin couldn't cure Brynn,
0:46:54 > 0:46:57he could tackle this particular problem.
0:46:57 > 0:47:00He prescribed her antihistamine drugs.
0:47:04 > 0:47:10I'm on a continuous infusion of IV Benadryl into my chest,
0:47:10 > 0:47:13which makes me a little less reactive.
0:47:13 > 0:47:16I would not be alive without antihistamines.
0:47:16 > 0:47:19Brynn's severe condition is rare
0:47:19 > 0:47:22but Dr Afrin was beginning to suspect
0:47:22 > 0:47:25that mast cell mutations may be responsible
0:47:25 > 0:47:28for a number of unexplained illnesses.
0:47:30 > 0:47:36Perhaps as many as 17% of the general First World population
0:47:36 > 0:47:40may have a mast cell activation syndrome.
0:47:41 > 0:47:44He suspects it could be the cause of other conditions
0:47:44 > 0:47:46that involve inflammation,
0:47:46 > 0:47:50like chronic fatigue syndrome and irritable bowel syndrome.
0:47:51 > 0:47:57Just the very notion that there is a disease
0:47:57 > 0:48:00that has the potential to cause
0:48:00 > 0:48:04what we clinically recognise as chronic fatigue syndrome
0:48:04 > 0:48:05or irritable bowel syndrome -
0:48:05 > 0:48:11this is great new potential for helping patients
0:48:11 > 0:48:16and furthering research and our understanding of these diseases.
0:48:16 > 0:48:19Dr Afrin is carrying out research
0:48:19 > 0:48:23to discover whether mast cells are also malfunctioning
0:48:23 > 0:48:25in people with these conditions.
0:48:25 > 0:48:28If so, this could lead to targeted treatments
0:48:28 > 0:48:31that would benefit millions of people.
0:48:32 > 0:48:36It's in the early stages but it's an exciting prospect
0:48:36 > 0:48:41and all through unlocking the secrets of one rare disease.
0:48:43 > 0:48:46Hi, Tasha. How are you?
0:48:46 > 0:48:49- Good, how are you?- I'm good.
0:48:49 > 0:48:52Through talking about her condition,
0:48:52 > 0:48:55Brynn's made friends around the world.
0:48:55 > 0:48:59I just wanted to thank all of you for helping me spread the word
0:48:59 > 0:49:06about these diseases and illnesses that desperately need awareness.
0:49:06 > 0:49:10Thank you for helping me do that. It means the world to me.
0:49:14 > 0:49:17Brynn's case shows that to comprehend fully
0:49:17 > 0:49:19how the machinery of our body works,
0:49:19 > 0:49:23we need to delve down into its tiniest units.
0:49:24 > 0:49:26And in our last remarkable story,
0:49:26 > 0:49:30we'll see how penetrating the hidden world of the cell
0:49:30 > 0:49:33can lead to the treatments of the future.
0:49:42 > 0:49:47This is Chris and Hugh Hempel, parents to twins Addi and Cassi.
0:49:49 > 0:49:53The girls suffer from a condition that affects how their cells work
0:49:53 > 0:49:56and that might have caused them to die in childhood,
0:49:56 > 0:49:59were it not for the extraordinary story
0:49:59 > 0:50:01of Chris and Hugh's search for a cure.
0:50:04 > 0:50:07The twins were always a little clumsy growing up,
0:50:07 > 0:50:12but we just chalked it up to, you know, being big kids.
0:50:13 > 0:50:16Everything seemed to be completely normal
0:50:16 > 0:50:19until the girls were about 18 months old.
0:50:19 > 0:50:23This couple noticed that their children were not developing
0:50:23 > 0:50:25at the same rate as others were.
0:50:27 > 0:50:30We were around other little kids that were just running faster,
0:50:30 > 0:50:33crawling, climbing on sofas, jumping around,
0:50:33 > 0:50:35and our kids didn't do that.
0:50:35 > 0:50:38At some point, it became evident
0:50:38 > 0:50:42that it wasn't...it wasn't just clumsy kids.
0:50:42 > 0:50:46And that began the roughly 18-month odyssey
0:50:46 > 0:50:49of getting a diagnosis for NPC.
0:50:52 > 0:50:55NPC is short for an inherited genetic disease
0:50:55 > 0:50:57called Niemann-Pick C.
0:50:57 > 0:51:01In its most severe form, it's a fatal condition.
0:51:05 > 0:51:11I like to describe Niemann-Pick type C as a childhood Alzheimer's.
0:51:12 > 0:51:14Essentially, children are born normally
0:51:14 > 0:51:17and then they progressively get worse.
0:51:17 > 0:51:21What's happened to them is that they're collecting cholesterol
0:51:21 > 0:51:24inside their bodies and it won't come out.
0:51:24 > 0:51:27The brain, effectively, begins to drown in cholesterol
0:51:27 > 0:51:30because the cholesterol won't come out of the cells,
0:51:30 > 0:51:36and so severe neuro degeneration is the main by-product.
0:51:37 > 0:51:40Chris and Hugh desperately needed a treatment
0:51:40 > 0:51:43to reverse or at least slow the disease.
0:51:44 > 0:51:46But that treatment didn't exist.
0:51:48 > 0:51:51Well, it's an unimaginable diagnosis,
0:51:51 > 0:51:54to learn that your kids have a fatal disease,
0:51:54 > 0:51:58and then to find out that there are no medications and no treatments.
0:52:00 > 0:52:04Now, I think most parents, given this news,
0:52:04 > 0:52:09would probably just try their best to accept their fate.
0:52:09 > 0:52:12Almost certainly, I think that's what I would do, even as a doctor.
0:52:12 > 0:52:17But this couple are different and they refused to do that.
0:52:18 > 0:52:24Chris and Hugh chose to fight NPC but they were starting from scratch.
0:52:24 > 0:52:28Neither of them were doctors, so they had to understand
0:52:28 > 0:52:32exactly what was happening inside Cassi and Addi's bodies,
0:52:32 > 0:52:37and this meant getting to the bottom of some pretty complex mechanisms
0:52:37 > 0:52:39happening inside their cells.
0:52:43 > 0:52:47Cholesterol is normally processed inside the lysosome,
0:52:47 > 0:52:52a part of the cell that digests substances we need to survive.
0:52:54 > 0:52:58But with NPC, this process goes wrong.
0:52:58 > 0:53:03Cholesterol accumulates inside the lysosome to toxic levels...
0:53:05 > 0:53:07..until the cell eventually dies.
0:53:10 > 0:53:13It's this that makes the disease so devastating.
0:53:17 > 0:53:21Chris was determined to learn all she could about NPC.
0:53:23 > 0:53:27It led her to a tantalising research project
0:53:27 > 0:53:30at the University of Texas Southwestern.
0:53:30 > 0:53:35Research suggests a substance called cyclodextrin could halt
0:53:35 > 0:53:37and reverse Niemann-Pick in mice.
0:53:37 > 0:53:40She shared her findings with the doctor
0:53:40 > 0:53:43who first diagnosed the twins, Caroline Hastings.
0:53:43 > 0:53:46I think it was probably just a matter of weeks later,
0:53:46 > 0:53:48Chris Hempel called me and said,
0:53:48 > 0:53:52"I want to get that drug and give it to my children. Will you help me?"
0:53:53 > 0:53:56Cyclodextrin is essentially a sugar compound
0:53:56 > 0:53:58and it's used in all kinds of products,
0:53:58 > 0:54:03ranging from toothpaste to fat-free butters.
0:54:03 > 0:54:06Millions and millions of people are exposed to cyclodextrin
0:54:06 > 0:54:08every single day.
0:54:11 > 0:54:14Cyclodextrin is a ring of sugar molecules.
0:54:14 > 0:54:17When two of these rings join up, they form a cone shape.
0:54:17 > 0:54:21This cone structure is perfect for grabbing cholesterol
0:54:21 > 0:54:23and carrying it away from the lysosome.
0:54:30 > 0:54:35But it's not a drug - or it wasn't when Chris found out about it -
0:54:35 > 0:54:37a drug that was in a form
0:54:37 > 0:54:40that could be taken to treat any kind of illness.
0:54:42 > 0:54:46Initially, we tried to feed it to the girls, which didn't work.
0:54:46 > 0:54:49And then we realised, "We actually have to make a drug now
0:54:49 > 0:54:52"that has to go into the bloodstream and the brain."
0:54:52 > 0:54:55So, we hired a team of people from around the world.
0:54:57 > 0:54:59Dr Hastings was willing to help us.
0:55:00 > 0:55:03Chris and Hugh both felt strongly
0:55:03 > 0:55:07that, since they knew that their children were going to die,
0:55:07 > 0:55:09they felt that they could not live with themselves
0:55:09 > 0:55:12if they did not take extraordinary risks
0:55:12 > 0:55:15and efforts to keep them alive.
0:55:17 > 0:55:20Aided by Dr Hastings and a team of experts,
0:55:20 > 0:55:23the Hempels fast tracked science.
0:55:23 > 0:55:28In 2010, the Federal Drug Administration granted permission,
0:55:28 > 0:55:31on compassionate grounds, for the Hempels to begin treatment.
0:55:33 > 0:55:37We started out doing what are called intravenous treatments,
0:55:37 > 0:55:41where the drug is just going directly into the bloodstream...
0:55:43 > 0:55:46..only later to find out that it doesn't really cross
0:55:46 > 0:55:49from the bloodstream into the brain very well.
0:55:49 > 0:55:52So, today, the twins get the treatment
0:55:52 > 0:55:56into their spinal column and also into their bloodstream.
0:55:58 > 0:56:01Chris and Hugh were told, in no uncertain terms,
0:56:01 > 0:56:04that their girls would die by the age of seven.
0:56:04 > 0:56:07And yet, here they are, almost 13 years old.
0:56:09 > 0:56:12If the twins weren't receiving the cyclodextrin,
0:56:12 > 0:56:15I think we're both sure that they wouldn't be with us today,
0:56:15 > 0:56:19so we're absolutely positive that it's helped them.
0:56:20 > 0:56:23And Chris and Hugh have noticed some positive changes.
0:56:23 > 0:56:28They were almost deaf, you know, very severe hearing impairments,
0:56:28 > 0:56:31before we started the cyclodextrin.
0:56:31 > 0:56:34So we saw a big bounce in positive hearing.
0:56:36 > 0:56:39We used to walk in the room, the kids didn't even look up.
0:56:39 > 0:56:41And now they look up,
0:56:41 > 0:56:44and so it definitely has had a positive impact.
0:56:47 > 0:56:51It's unclear how much of the damage caused by NPC
0:56:51 > 0:56:53cyclodextrin can reverse,
0:56:53 > 0:56:56but the Hempels are now driven to share their knowledge
0:56:56 > 0:57:00with parents and scientists all over the world.
0:57:02 > 0:57:05We get calls every week from families
0:57:05 > 0:57:09and they're just getting diagnosed, they're in the same spot we were,
0:57:09 > 0:57:11and now there's an option for them
0:57:11 > 0:57:13and it's that little glimmer of hope.
0:57:13 > 0:57:18And that's... A lot of times, that's all you really need.
0:57:20 > 0:57:24The Hempels continue to advance medical science.
0:57:24 > 0:57:28All affected by NPC now have hope.
0:57:39 > 0:57:43What all these cases show is that we're constantly learning
0:57:43 > 0:57:45about the intricate machinery of our anatomy,
0:57:45 > 0:57:49through the stories of courageous people whose bodies are different.
0:57:52 > 0:57:56And what's really exciting for me, as a doctor,
0:57:56 > 0:57:58is that every nuance and flaw we discover
0:57:58 > 0:58:03will drive the progress of medicine into the future.
0:58:05 > 0:58:07Next time, we'll discover
0:58:07 > 0:58:11why this man's bones have inspired experiments in space,
0:58:11 > 0:58:15why this woman has two wombs
0:58:15 > 0:58:20and how this boy's cells were re-engineered to save his life.
0:58:20 > 0:58:24It's a world full of extraordinary humans.