Episode 4 Incredible Medicine: Dr Weston's Casebook

We're discovering astonishing things about the human body

all the time, through people who are different from most.

I'm Gabriel Weston.

As a surgeon, I've spent years studying the human body

and the secrets of how it works are often revealed

by the most rare and surprising of cases.

So, I've searched the world to find these extraordinary people

and bring you their stories.

This is my heart.

I'm the only one that has this.

I'm Jordy Cernik and I can't feel fear.

My name is Harnaam Kaur and I'm a fabulous bearded lady.

With the help of the doctors that treat them,

and some of the world's leading scientists,

I'll be uncovering exactly what makes their bodies unique.

I'm going to show you the hidden processes

that make them exceptional.

Just look at that!

I'll discover how they're leading us to the cures of the future.

When we make a breakthrough like this, it is very exciting.

And I'll use the latest technology

to uncover the secrets of their bodies

and reveal how all of these cases are giving us a new understanding

of the most amazing natural machine on the planet - the human body.

'The human body is a wonder of the natural world -

'a beautifully crafted piece of precision engineering

'with thousands of intricate parts working in perfect harmony.'

It's only when we test a machine to its limits

that we know what it's capable of.

In this programme, we're going to delve into the secret inner workings

of the human body through some truly extraordinary cases.

We'll discover why this woman had two hearts,

why this woman's body can bend in ways no-one else's can

and how this man can produce sounds that seem impossible.

Through these cases,

I'm going to reveal a hidden world of astonishing mechanics,

materials and intricate working parts,

unsurpassed by anything we humans have invented.

And our first few cases are people with some surprising variations

to the fundamental human model,

who can perform feats that seem almost superhuman.

MUSIC: Born To Run by Bruce Springsteen

One time, I signed up for a 200 mile, 12-person relay race,

just to do it solo.

I actually ran 50 marathons in all 50 of the United States

in 50 consecutive days.

My name is Dean Karnazes

and I've run through three days and three nights without stopping.

# Baby, we were born to run. #

The night of my 30th birthday, and I'm in a bar

and I'm doing what we do, here in America, on our 30th birthdays.

I was drinking with my buddies.

I had a really comfortable, cush job in San Francisco

as a young corporate executive.

I had all the perks you would imagine - a company car,

stock options, health insurance - but I was miserable.

And I just had this epiphany - leave the bar.

And at 11 o'clock at night, drunk,

and ran 30 miles, straight through the night that night.

I remember, when I ran, that was the only time I really felt alive

and when I felt most alive is when I was struggling

and in great pain and trying to persist.

And something almost primordial bubbled up that night.

That was 24 years ago

and you could say that Dean hasn't stopped running since.

He's completed some of the toughest endurance events on the planet,

from the South Pole to the Silk Road.

He's the ultimate ultra-marathon man.

So, some of the races I've run have been 50 miles,

100 miles, 200 miles.

Dean decided to test how far he could run without stopping.

And after actually making it 350 miles

in over 81 hours of continuous running,

I think I found my limit.

Cos that third night without sleep was really vexing.

I got through the first two nights with no sleep OK,

but that third night, I was hallucinating,

I was falling asleep as I was running

and I thought, "This is kind of the functional limit

"that a human can go, at least myself."

So, if it weren't for the minor inconvenience of having to sleep,

Dean could just keep running, apparently without needing to stop.

Here is a man who seems to completely redefine what it means

to push your body to the limits, but how is this humanly possible?

My name is Anthony Luke

and I'm the Director of Primary Care Sports Medicine,

here at the University of California in San Francisco.

For Dean, I think he's the epitome of the ultra-marathon athlete.

I don't think I've heard of anyone

put as many miles on his body as he has.

To try to get to the bottom of Dean's extraordinary abilities,

Dr Luke and his colleague, exercise physiologist Dr Nicole Pinto,

have invited him to their lab.

Put your heart rate monitor on.

The team are looking at two indicators of Dean's fitness.

The first is how efficiently his body uses oxygen.

Dean's doing really well so far.

We have him at some lower stages and as we ramp him up,

he'll probably get more tired.

Are you ready for the next stage, Dean? Move him up to 7.7.

As well as analysing his oxygen use, they're also testing the levels

of a chemical in his blood called lactate.

Are you doing OK?

When we're exercising, there are all these processes occurring

where we're metabolising or breaking down nutrients

and those processes have by-products.

Lactate is a by-product of exercise.

It's a substance which is built up in the muscles

and when it reaches a certain point,

it has to be cleared from the muscles into the blood.

I sort of think of lactate as being the thing

that causes that burn when you do exercise.

Are you ready for the next stage, Dean? Give me a thumbs-up. Good.

And we're going up.

Anthony and Nicole take regular blood tests

to measure Dean's lactate levels.

-17, very hard.

-OK.

-Going up.

-Let me know when, Nicole.

-And go ahead.

Are you OK, Dean?

The team are also taking a detailed look at the way that Dean runs.

Place markers here on your lower back and upper back.

We're testing Dean's biomechanics by using a 3-D marker system.

As they analyse the results,

the team hope to find the secret of Dean's extraordinary ability.

-These are the results?

-Yeah, how are you feeling now?

-Rested a little bit?

-I've recovered now, yeah.

-OK.

So, first we're going to look at heart rate

-and we're going to do that in comparison to speed.

-Mm-hmm.

So, if you look here at the blue line, that's your heart rate

and we see a nice smooth increase, which is expected

for an ultra-endurance athlete.

Dean is at peak fitness.

But this alone doesn't explain

why he can run such superhuman distances.

So, now the team analyse his technique.

This is just a visual 3-D reconstruction

of your skeleton actually running.

You do kind of flex at the knee

-a little bit more than someone else.

-I see that, yeah.

That'll have some advantages when you're kind of absorbing shock,

as well as your efficiency to kind of push yourself back.

Dean's efficient technique will help keep him going

but it can't explain why his muscles don't eventually tire.

The scientists hope they might find a clue

in the final results from the lactate test.

Most of us hit a point where our muscles start to burn.

This is known as our lactate threshold,

when lactate is being produced faster than we can get rid of it.

But the results suggest Dean is different.

You're starting at a nice low level.

You start exercising and, actually, your blood lactate level dips

and that's probably because your heart rate's kind of going,

it's moving blood and your body's very efficient at clearing that.

You're holding a nice low blood lactate level at your sweet spot.

-Yeah.

-Where you like running,

where you run all those hundreds of miles, you're very economical.

So, this is the secret of Dean's amazing abilities.

His blood is able to quickly clear lactate from his muscles

which, in most of us, would make it too painful to carry on.

People always ask me, "How long are you going to keep this up?"

I always tell people, "My finish line is a pine box."

By around 50, we see people slowing down a little bit,

people may be getting a little more aches and pains or even problems.

Certainly, for Dean, he's continued to do these things

for the last ten years, at least that I've known him.

I don't see any signs of slowing down.

I still love to run as much as I did

and if I wake up one morning and that passion and that fire's gone,

I'll stop running, but right now, it's still white hot.

So, I just love exploring the limits

and I think I'm going to keep doing it as long as I can.

What enables Dean to power through these incredible feats of endurance

are these - his skeletal muscles.

And, in fact, it takes about 200 of these muscles

just to take one single step.

All over our bodies, even where you wouldn't expect them,

there are muscles at work,

keeping every part of our machinery moving and functioning.

Now, I trained as an ear, nose and throat doctor

and I spent a lot of my time focussed on a group of muscles

that most people have probably never heard of.

These are the muscles of the larynx or voice box.

Together with our tongue,

these muscles work collectively to do something almost magical.

They produce the very precise set of vibrations in the air

that give each of us our unique voice.

But the next extraordinary person we're about to meet

can use this machinery to make sounds that should be impossible.

HE SINGS TWO NOTES SIMULTANEOUSLY

This man is a professional singer. But he has no ordinary voice.

HE SINGS ODE TO JOY WITH TWO SIMULTANEOUS RUNS OF NOTES

My name is Wolfgang Saus and I can sing two notes at the same time.

This mysterious style of singing

is known as polyphonic or overtone singing.

Most of us can make only one note at a time,

so how is it possible to produce two?

Over 30 years ago, Wolfgang set out to answer that very question.

Back then, he was a successful research chemist,

for whom singing was a hobby.

One day, he opened his mouth

and what came out astonished him.

HE SINGS TWO SIMULTANEOUS RUNS OF NOTES

I was amazed about the sound

and to hear a full orchestra in your own voice is absolutely amazing.

But he had absolutely no idea

how he was producing these extraordinary sounds.

So, I went home and tried many things.

HE MAKES TRILLING SOUND

I first to the mirror and looked into my throat,

but this was a stupid idea. I didn't know how my voice worked.

I tried something with my tongue and suddenly there was an overtone

and then it was lost again and then I couldn't find it.

HE TRILLS

'Wolfgang gave up his research job

'and decided to turn his unusual singing talent into a new career,

'and to perfect his technique,'

he wanted to uncover the secret

of exactly how he was making these astonishing sounds.

'I think I'm a scientist'

and I want to know how things work.

And there was one man who could help him unlock that mystery.

Professor Bernhard Richter is the head

of the Freiburg Institute for Musicians' Medicine.

He's a trained opera singer and a doctor.

Open your mouth, please.

Science is art and art is science, for me,

so I try to help singers understand

what's going on inside their bodies.

And Professor Richter has a few state-of-the-art tools to help him.

WOLFGANG SINGS A SINGLE NOTE

This software analyses sound

and helps visualise the notes being produced.

Please make just a normal sound of a normal singer,

opera-like singer, you know.

WOLFGANG SINGS A SINGLE NOTE

When we sing normally, we produce

lots of different frequencies at once,

shown by the different bars here.

Our brain combines these different frequencies

and we hear a single note.

Now, can you please do, for me, the overtone singing?

WOLFGANG SINGS WITH OVERTONES

But Wolfgang is able to make us think

he's singing two notes at the same time.

He does this by filtering out some overtones and making others louder.

What you heard was all the time the same fundamental frequency,

but we heard the changing of the overtones.

RECORDING OF WOLFGANG SINGING WITH OVERTONES

To work out how Wolfgang is able to do this,

Professor Richter put him into an MRI scanner and made him sing.

First, he's looking at what happens when Wolfgang sings normally.

Now, the most important thing is the shape of the tongue.

You can see that the tongue is quite flat here

and there is a narrowing

between the back of the tongue and the pharynx wall here.

When Wolfgang sings normally,

his tongue creates a single resonance chamber.

This is the black area on the scan,

essentially a chamber full of air where sound waves resonate -

in this case, producing a single sound.

But when he switches to overtone singing,

Wolfgang does something completely different.

RECORDING OF WOLFGANG SINGING WITH OVERTONES

You can see clearly how the tip of his tongue is going upwards

and creating this chamber underneath the tongue.

The black column there is the air and the more grey are the muscle.

And you can see, for the different overtones,

he has a different tongue shape here.

Very impressive how much he can move, actually, his tongue.

So, his tongue is creating two different resonance chambers

and that has a profound effect on what we hear.

There's a completely different vocal sound

and this is what you perceive. You perceive two tones.

Actually, I'm still singing the same as before,

but the brain makes two tones out of it.

HE SINGS WITH OVERTONES

This is the secret to singing two notes at the same time.

Wolfgang alters the shape of his mouth

to amplify particular frequencies.

In theory, it's something that anyone could do,

but it takes years of dedicated practice.

It's fantastic to see, after many years of singing

and investigating and trying to find out

what happens in overtone singing,

to, in the end, see what the tongue does and it's...

-It's not imagination. It's more reality, you know.

-Yeah.

Wolfgang's rare skill reveals how we can consciously manipulate

our muscles to achieve extraordinary things.

Our bodies are full of moving parts that are working all the time.

And it's often when something goes wrong

that we see what they're really capable of,

as we'll discover in our next few cases.

Take the heart, for example.

In a single day and 100,000 beats,

this heart can pump 2,000 gallons of oxygen-rich blood

around 60,000 miles of vessels.

'And in one of the most astonishing cases I've come across,

'a life-threatening problem with one girl's heart

'has changed our understanding of this most vital organ.'

The fact that this young woman is alive

is one of the most dramatic successes

in recent medical history.

My name is Hannah Clark and I used to have two hearts.

Soon after Hannah was born, her parents, Liz and Paul,

began to worry that something might be wrong.

It was definitely the screaming. It was piercing.

There was never a time that she was a well baby.

A chest X-ray when she was eight months old

revealed Hannah had an enlarged heart,

a condition called dilated cardiomyopathy.

BABY CRIES

As a result, her heart struggled to pump blood around her body.

Every time you would think it was not so bad,

and then something else would happen,

and then it would get worse and worse.

Liz and Paul were told Hannah would need a heart transplant.

Consultant cardiologist Dr Dirk Wilson first met Hannah

when she was only eight months old.

She weighed less than 10kg and the likelihood of finding a donor heart

for an infant of that size is actually quite small.

Without a heart exactly the right size for Hannah,

the doctors decided to try

a different and unusual kind of transplant.

It's called a heterotopic or piggyback transplant.

Instead of removing Hannah's heart, the doctors would leave it in place

and implant a second one from a donor.

The idea was that both hearts would then work together

to pump blood around her body.

Hannah was just two years old when she had her piggyback transplant.

They told us if she didn't have the transplant when she did,

she wouldn't have made it. She was that ill.

But the operation was a success.

Her two hearts beating together worked better

than anyone could have imagined.

But when Hannah was six, she found herself back in hospital.

She went ill one day and these glands started to pop up,

-didn't they?

-Her kidneys started failing. She was really ill.

As with any transplant,

there was a risk that Hannah's body would reject her new heart,

that her immune system would see it as something foreign

and her body would attack it.

So, for this reason, ever since her transplant,

she'd been taking drugs to suppress her immune system.

But these had left her vulnerable to illness

and she'd developed life-threatening complications.

They called us in the room and they said, um...

.."We think she's only got 12 hours to live."

Hannah received lifesaving treatment

and her doctors reduced her dose of anti-immunity drugs.

Her immune system began to recover

but that had a devastating side effect.

By reducing the anti-immunity drugs,

it meant that the heart was being rejected

and its function had gone down - the donor heart.

Slowly, over time, the donor heart that had kept Hannah alive

was being attacked by her own body...

..a situation that could be fatal.

But then, doctors noticed something remarkable.

Hannah's own heart now appeared to be recovering...

..something they'd never seen a damaged heart do before.

And it gave them a radical idea.

We started to wonder, perhaps if they took out the donor heart,

wouldn't that be the way forward?

Would it be the right thing to remove the donor heart

and would that actually improve Hannah's situation?

The doctors decided to go ahead with this groundbreaking operation.

In February, 2006, they removed the donor heart,

leaving Hannah's own heart to function without any assistance.

It was a world first and nobody could predict the outcome.

-TV NEWS REPORT:

-A hug from her mum,

as Hannah Clark is overcome by emotion at a press conference.

The heart is not showing any signs of deterioration.

As a matter of fact, it's getting better and better.

After just five days in hospital, Hannah returned home.

I didn't expect how she came out of it so quick.

It was just lovely to see,

cos we didn't think that was going to happen.

Hannah has been on a remarkable medical journey,

one that's changed the way

doctors approach life-threatening heart problems.

If there's a chance a diseased heart might recover if rested,

as happened with Hannah, doctors are now less likely

to perform a transplant as a first option.

Instead, they may try a robotic device

to assist the heart and give it a chance to recover.

Hannah's case has shown us that even in situations where we think

there is no hope of recovery, recovery can occur.

Hannah is now 23 and has a baby of her own.

I always think about the doctors and the surgeons

who done my operations and stuff, really.

I wouldn't really be here without them.

They practically brought me back to life not just once - twice, really.

I'm really proud and really glad I had the doctors I had.

'As a surgeon, I can't help but be excited by cases like Hannah's,

'where a life-threatening medical problem is solved

'by pioneering surgery.

'But sometimes, things go wrong in our bodies that don't need fixing.

'Occasionally a fault can even give us an edge.'

In our next case,

a flaw in the finely-tuned machinery of her body,

has given one woman the ability to move in ways

that, for the rest of us, are completely impossible.

My name is Claudia Hughes and I can bend in ways that no-one else can.

Like lots of children, Claudia loved dance and gymnastics,

but people around her noticed that she was no ordinary dancer.

Claudia was different.

I remember getting a ballet book from my mum

and there was, like, a picture of a girl doing splits in there

and I was, like, "That's so cool. I'm going to try that."

I could just do the splits straightaway.

Claudia found that she was naturally bendier than most people.

We used to have to do stretches at the beginning of a dance class

and we had to do this one exercise

where we were just kicking our leg up behind us.

And my leg just went all the way round

and gave me this massive black eye.

Claudia now performs professionally.

I'm a full-time contortionist. This is my career.

I'm the only British contortionist

to be able to do the spinning Marinelli bend.

Recently, I've been proclaimed Britain's bendiest woman,

which is quite an achievement.

When you see Claudia in action, it's completely mind-boggling

and the obvious question is, how on Earth can she do it?

What is it about her body that enables her to bend in ways

that would be impossible for most of us?

Dr Emma Redding is Head of Dance Science

at the Trinity Laban Conservatoire of Music and Dance.

I'm really interested in hypermobility.

That's different to flexibility.

Flexibility refers to the range of motion at a joint,

and dancers, for example, and gymnasts have good flexibility.

But hypermobility is something different.

That's when a joint goes beyond its sort of extension, its normal range.

Dr Redding has invited Claudia to her lab

to try to get to the bottom of her extraordinary abilities.

She uses a device called a goniometer

to discover just how hypermobile Claudia really is.

-Is that good?

-Yeah.

-OK, great.

Interestingly, the elbows -

-you could extend those 17 degrees beyond normal.

-Mm.

And your knees, 17, 18 degrees beyond a normal person's.

Claudia's range of movement goes far beyond the normal limits.

It's greater than in anyone Emma has seen before,

including highly trained and flexible dancers.

And Dr Redding knows the likely cause.

Essentially, if you've been born with hypermobility,

then it probably means that the connective tissues

that surround those joints are lax.

They're looser than normal joints.

Claudia is far bendier than most of us

because there's something wrong with her ligaments

which hold her joints together.

They're made from a material called collagen.

But in Claudia, it's weaker than it should be.

This is what gives her superhuman abilities, but they come at a price.

Individuals with hypermobile joints have to work harder

-to stabilise those joints.

-Yeah.

There's more muscle tension created during the day

-to sort of maintain that stability.

-I do get tired really easily.

In a sense, you've been expending more energy during the day

than a normal person.

And being so bendy also carries a risk.

Hypermobile joints can twist very easily

and often can suffer from injury.

With weak ligaments, Claudia is at risk of hurting herself

but, remarkably, she rarely gets injured.

To find out why this might be, Dr Redding carries out another test.

-I'm just going to take a quick measurement.

-OK.

Keep your arm there for me.

And then you try and match the angle with the other arm.

She's measuring Claudia's awareness

of the position of her body in space,

an ability called proprioception.

So, when we positioned your arm in a particular place,

we asked you to close your eyes

and replicate that joint on the other side.

-Yeah, I found that quite easy.

-And you replicated that angle very well.

So, it does seem that you have good proprioception in your upper body.

Your brain is registering that it's OK for your body

to be going to those extreme ranges of motion

cos it can sense where they are.

Right, OK.

Claudia's awareness of her body helps her to stay in control

of her bendy joints and so push her body to its absolute limits.

I love trying new contortion stuff around the house,

partly because I'm training

and doing household work at the same time.

Sometimes, if I have friends over, it's always a bit of a party trick

to, like, come out of a cupboard or something and scare them.

I'm just having a great time at the moment.

I just want to do it for as long as my body can

and then I'll see what happens.

Claudia's extraordinary ability to bend her body

is only physically possible because of an abnormality

in one of the most prevalent and important materials

in the human body - collagen.

And I can show you some of its special properties with this egg.

But first of all, I need to get rid of its hard shell,

so I'm just going to put this into a bowl of vinegar, which is an acid.

If I leave it there for long enough, what I'll end up with is this -

this amazing thin membrane, which is made of collagen

and which actually gives the egg its perfect shape,

since it's the shell that just grows on top of this.

But the collagen isn't just making the egg look smooth and beautiful,

it can also do something else which is really cool.

It's the combination of strength and flexibility in the collagen

that allows the egg to bounce up and down like that.

What I'm going to do now is dissect this collagen membrane

and empty it out, and the contents are spilling out into this bowl.

And what this leaves me with is this amazing collagen-rich membrane

round the outside, which is kind of very, very strong,

but also stretchy and tough.

It's these properties that make it perfect for stabilising our joints

and controlling their range of movement.

But they also play a key role in another part of our body - our skin.

And there's one fascinating case I've come across

that's shown me just how important this is.

It's one of the most moving I've seen.

For most people, lunch at a cafe with friends is a simple pleasure.

For Paul, it requires an almost superhuman effort

because of a condition he's had since birth that affects his skin.

My name is Paul Martinez and I'm from Stockton, California.

I have a condition called epidermolysis bullosa.

They call it EB for short.

My skin is very fragile, like paper.

Epidermolysis bullosa, or EB, is a genetic condition

that makes the skin incredibly delicate.

Our skin is made up of layers that, in most people,

are anchored together.

But in Paul, the layers are only loosely connected,

so they rub against each other.

Any small bump can lead to a blister.

The blister then turns into a second or third-degree burn.

My skin is always hurting, like it's on fire.

The hands and feet are particularly vulnerable to damage

because they're constantly subjected to pressure and friction.

In Paul's case, his fingers are now encased in scar tissue.

People with EB are also more likely

to develop skin cancer as young adults.

It's a condition for which there's, as yet, no cure.

Doctors can prescribe drugs to help deal with the constant pain,

but Paul chooses not to take them.

I just feel that I value my mind a lot.

I wasn't blessed in many aspects, but I feel I was blessed in my mind.

So, I don't want to take that away.

Paul has refused to let EB hold him back.

He gained his high school diploma

and attended the prom just like all the other kids,

and then later graduated from college

with a degree in business.

'Any injury or disease can be risky or painful,

'but when the problem involves your skin,'

the material that covers your whole body,

there isn't a single part of you that isn't affected.

As a doctor, I find it hard to understand

how you'd even begin to grapple with a condition like Paul's.

But he's been working with leading scientists

who have been uncovering exactly what causes EB

and he's become one of the very first in the world

to try out a pioneering new treatment.

At Stanford University, teams of scientists have spent decades

trying to decipher the riddle of EB.

Today, the research is led by dermatologist Dr Peter Marinkovich.

It's a very terrible existence for these patients,

to live with pain all their lives

and then face the prospect of having to have

this very severe, often fatal, carcinoma

as they approach their early adulthood.

The plight of EB sufferers like Paul is a driving force

for researchers here at Stanford.

The problem lies in the structure of the skin.

Skin has different layers.

The top layer is the epidermis. That's the bit that you can touch.

Underneath that is the dermis, where new skin cells are formed.

And in between those two layers,

there's something called the basement membrane.

The basement membrane's like a molecular glue.

You could think of it as links on a chain and there's different proteins

that make up each of the different links.

And when any of those links is damaged,

then the skin will fall apart.

In Paul's form of EB,

one of these key proteins is damaged - collagen VII.

It means the basement membrane doesn't hold

the layers of Paul's skin together as it should.

This is why the layers rub against each other,

causing the pain and blistering he experiences.

The scientists here at Stanford have discovered that the reason

for the damage to collagen VII is a faulty gene.

And this has led to a breakthrough.

For the first time, there's a potential new treatment for EB,

by taking some skin cells from the patient,

correcting the genetic fault,

and then growing them some new, healthy skin.

The technique is known as gene therapy.

A clinical trial is now under way, overseen by specialist Dr Jean Tang.

We've invested 20 years to develop gene therapy.

So, patients with EB lack collagen VII.

They have an abnormal collagen VII gene.

And in this clinical trial, we take a small biopsy of their skin.

We grow out the skin cells in a laboratory Petri dish

and then we use a virus to infect those cells

with the collagen VII gene.

Viruses are a standard way, used in gene therapy,

to carry healthy DNA into human cells,

because they can penetrate the cell without damaging its structure.

In this instance, the virus carries a working version of the gene

for collagen VII into the patient's skin cells in the lab.

From that, they're producing small skin grafts

which now have this essential missing protein

in the basement membrane,

which is anchoring the epidermis and the dermis together.

It takes about 30 days to grow up enough cells

to make about six grafts

and then we bring the patient back into the operating room,

give them general anaesthesia

and now are able to transfer these genetically corrected skin cells

onto their chronic wounds.

Over the past three years, the team have treated four patients

with this groundbreaking therapy, including Paul.

The patients had chronic wounds that were unhealed for years,

and now, after the gene-corrected grafts,

these wounds are closed, they're healed up and the patients,

in many instances, can now walk on their wounds.

After the grafting, Paul showed some amazing results.

He was walking on these areas

where he'd never walked without pain before

and he was able to withstand blistering.

He did amazingly well after the trial.

'I like to hang out with my friends.

'We get together and play card games and stuff like that,

'so it's really fun just to get out and socialise and laugh'

and have a good time.

Paul knows that taking part in the trial isn't going to cure him,

but he has a longer-term goal.

'I did it for the future of EB.'

It is a very excruciating disease

that I don't want anybody to go through,

so, if I can do my small part and, you know, help find a cure someday,

then I have no, er, no doubt in just doing it.

Paul's story, more than any other case, makes me appreciate

the extraordinary materials that make up our body.

'But at a deeper level than anything we've seen so far,

'what keeps the machinery of our body working day and night

'are hidden systems that operate on the microscopic scale.

'And our next case involves one of the most important of these -

'our immune system.'

It's our body's own in-built

emergency response and repair system.

And perhaps the best way to understand

just what an extraordinary piece of natural engineering it is

is to see what happens when the system itself goes wrong.

Right now, you wouldn't know

that I was dealing with anything out of the ordinary,

but other days, I look...like a corpse.

Life for 22-year-old Brynn can be a little unpredictable.

It's a question of hoping for the best and preparing for the worst.

Because every day brings a new battle and a new enemy.

I'm allergic to everything.

I am allergic to most fruits and vegetables,

nuts, strong perfumes, cigarette smoke...

And the list goes on.

Soy, corn, egg, milk, garlic... She's even allergic to the sun.

The allergies change every day - or the triggers, I should say.

Her reactions are so severe, Brynn avoids eating.

She relies on a feeding tube for her nutrients.

This is the feeding bag.

But even this can't protect Brynn.

This goes into my intestines.

She's constantly vulnerable to attack and when it happens,

she doesn't just suffer the odd sneeze or itchy rash.

She goes into anaphylactic shock.

Anaphylaxis is a serious life-threatening allergic reaction.

You can't breathe,

you feel like your heart's going to either pound out of your chest

or stop completely.

If it progresses far enough, then it can lead to death.

It's a life lottery Brynn's been forced to play since childhood,

her mystery reactions steadily worsening as she's grown older.

I went from always active, always on my bike,

third-degree black belt taekwondo.

Then that kind of was taken over by the illness.

A lot of doctors had a hard time

explaining the symptoms that I suffered.

It's very obvious that I had something seriously wrong,

but no-one could explain what it was.

Having allergic reactions to pretty much everything,

and with her doctors baffled, it would have been easy for Brynn

to just give up and accept that her body was never going to work

the way it should.

But she and her family were determined to persevere

and get to the bottom of this mysterious condition.

The man who would help them is Dr Lawrence Afrin,

a specialist in blood disorders.

Brynn's case is actually severe.

The symptoms she had when I first saw her went well beyond allergies.

The essence of this disease, actually,

is much more chronic inflammation.

Inflammation isn't a bad thing.

It's our body's way of fighting infection and helping us heal.

But too much at the wrong time and wrong place

can have a serious impact on our bodies.

Something was making Brynn's body overreact.

And Dr Afrin suspected the attack wasn't coming from the outside

but from an enemy within -

a particular type of white blood cell, known as a mast cell.

Mast cells stand guard, looking out for insults upon the body, assaults.

And it can be infections, sometimes it's trauma.

There's no other defence system in the body that reacts as quickly,

as instantaneously as the mast cell.

Mast cells are present in nearly all of our tissue.

They swing into action to defend our body from infection,

using an array of chemical defences called mediators.

The most potent is histamine.

The dominant effect from histamine is itching.

When we suffer an insect bite,

we know that there's a local reaction -

redness and some swelling and some itching.

Histamine is closely involved in producing that sensation.

But, unfortunately, sometimes we get the situation

where the mast cells start misbehaving

and they start putting out the wrong mediators,

sometimes when there's not even any trigger at all.

Brynn's mast cells were pretty dysfunctional.

It's a condition known as mast cell activation syndrome.

Brynn's mast cells were releasing too much histamine

and causing inflammation when it wasn't needed.

While Dr Afrin couldn't cure Brynn,

he could tackle this particular problem.

He prescribed her antihistamine drugs.

I'm on a continuous infusion of IV Benadryl into my chest,

which makes me a little less reactive.

I would not be alive without antihistamines.

Brynn's severe condition is rare

but Dr Afrin was beginning to suspect

that mast cell mutations may be responsible

for a number of unexplained illnesses.

Perhaps as many as 17% of the general First World population

may have a mast cell activation syndrome.

He suspects it could be the cause of other conditions

that involve inflammation,

like chronic fatigue syndrome and irritable bowel syndrome.

Just the very notion that there is a disease

that has the potential to cause

what we clinically recognise as chronic fatigue syndrome

or irritable bowel syndrome -

this is great new potential for helping patients

and furthering research and our understanding of these diseases.

Dr Afrin is carrying out research

to discover whether mast cells are also malfunctioning

in people with these conditions.

If so, this could lead to targeted treatments

that would benefit millions of people.

It's in the early stages but it's an exciting prospect

and all through unlocking the secrets of one rare disease.

Hi, Tasha. How are you?

-Good, how are you?

-I'm good.

Through talking about her condition,

Brynn's made friends around the world.

I just wanted to thank all of you for helping me spread the word

about these diseases and illnesses that desperately need awareness.

Thank you for helping me do that. It means the world to me.

Brynn's case shows that to comprehend fully

how the machinery of our body works,

we need to delve down into its tiniest units.

And in our last remarkable story,

we'll see how penetrating the hidden world of the cell

can lead to the treatments of the future.

This is Chris and Hugh Hempel, parents to twins Addi and Cassi.

The girls suffer from a condition that affects how their cells work

and that might have caused them to die in childhood,

were it not for the extraordinary story

of Chris and Hugh's search for a cure.

The twins were always a little clumsy growing up,

but we just chalked it up to, you know, being big kids.

Everything seemed to be completely normal

until the girls were about 18 months old.

This couple noticed that their children were not developing

at the same rate as others were.

We were around other little kids that were just running faster,

crawling, climbing on sofas, jumping around,

and our kids didn't do that.

At some point, it became evident

that it wasn't...it wasn't just clumsy kids.

And that began the roughly 18-month odyssey

of getting a diagnosis for NPC.

NPC is short for an inherited genetic disease

called Niemann-Pick C.

In its most severe form, it's a fatal condition.

I like to describe Niemann-Pick type C as a childhood Alzheimer's.

Essentially, children are born normally

and then they progressively get worse.

What's happened to them is that they're collecting cholesterol

inside their bodies and it won't come out.

The brain, effectively, begins to drown in cholesterol

because the cholesterol won't come out of the cells,

and so severe neuro degeneration is the main by-product.

Chris and Hugh desperately needed a treatment

to reverse or at least slow the disease.

But that treatment didn't exist.

Well, it's an unimaginable diagnosis,

to learn that your kids have a fatal disease,

and then to find out that there are no medications and no treatments.

Now, I think most parents, given this news,

would probably just try their best to accept their fate.

Almost certainly, I think that's what I would do, even as a doctor.

But this couple are different and they refused to do that.

Chris and Hugh chose to fight NPC but they were starting from scratch.

Neither of them were doctors, so they had to understand

exactly what was happening inside Cassi and Addi's bodies,

and this meant getting to the bottom of some pretty complex mechanisms

happening inside their cells.

Cholesterol is normally processed inside the lysosome,

a part of the cell that digests substances we need to survive.

But with NPC, this process goes wrong.

Cholesterol accumulates inside the lysosome to toxic levels...

..until the cell eventually dies.

It's this that makes the disease so devastating.

Chris was determined to learn all she could about NPC.

It led her to a tantalising research project

at the University of Texas Southwestern.

Research suggests a substance called cyclodextrin could halt

and reverse Niemann-Pick in mice.

She shared her findings with the doctor

who first diagnosed the twins, Caroline Hastings.

I think it was probably just a matter of weeks later,

Chris Hempel called me and said,

"I want to get that drug and give it to my children. Will you help me?"

Cyclodextrin is essentially a sugar compound

and it's used in all kinds of products,

ranging from toothpaste to fat-free butters.

Millions and millions of people are exposed to cyclodextrin

every single day.

Cyclodextrin is a ring of sugar molecules.

When two of these rings join up, they form a cone shape.

This cone structure is perfect for grabbing cholesterol

and carrying it away from the lysosome.

But it's not a drug - or it wasn't when Chris found out about it -

a drug that was in a form

that could be taken to treat any kind of illness.

Initially, we tried to feed it to the girls, which didn't work.

And then we realised, "We actually have to make a drug now

"that has to go into the bloodstream and the brain."

So, we hired a team of people from around the world.

Dr Hastings was willing to help us.

Chris and Hugh both felt strongly

that, since they knew that their children were going to die,

they felt that they could not live with themselves

if they did not take extraordinary risks

and efforts to keep them alive.

Aided by Dr Hastings and a team of experts,

the Hempels fast tracked science.

In 2010, the Federal Drug Administration granted permission,

on compassionate grounds, for the Hempels to begin treatment.

We started out doing what are called intravenous treatments,

where the drug is just going directly into the bloodstream...

..only later to find out that it doesn't really cross

from the bloodstream into the brain very well.

So, today, the twins get the treatment

into their spinal column and also into their bloodstream.

Chris and Hugh were told, in no uncertain terms,

that their girls would die by the age of seven.

And yet, here they are, almost 13 years old.

If the twins weren't receiving the cyclodextrin,

I think we're both sure that they wouldn't be with us today,

so we're absolutely positive that it's helped them.

And Chris and Hugh have noticed some positive changes.

They were almost deaf, you know, very severe hearing impairments,

before we started the cyclodextrin.

So we saw a big bounce in positive hearing.

We used to walk in the room, the kids didn't even look up.

And now they look up,

and so it definitely has had a positive impact.

It's unclear how much of the damage caused by NPC

cyclodextrin can reverse,

but the Hempels are now driven to share their knowledge

with parents and scientists all over the world.

We get calls every week from families

and they're just getting diagnosed, they're in the same spot we were,

and now there's an option for them

and it's that little glimmer of hope.

And that's... A lot of times, that's all you really need.

The Hempels continue to advance medical science.

All affected by NPC now have hope.

What all these cases show is that we're constantly learning

about the intricate machinery of our anatomy,

through the stories of courageous people whose bodies are different.

And what's really exciting for me, as a doctor,

is that every nuance and flaw we discover

will drive the progress of medicine into the future.

Next time, we'll discover

why this man's bones have inspired experiments in space,

why this woman has two wombs

and how this boy's cells were re-engineered to save his life.

It's a world full of extraordinary humans.