Episode 1 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.

Every one of us is built to the same fundamental and familiar blueprint.

We take for granted the shape and form of our body.

It's what makes us recognisably human,

shared across the species and the planet.

But there are some extraordinary people

who don't follow that universal plan.

In this programme, we'll discover

why this man doesn't have an ounce of fat on his body...

..why this woman is growing a second skeleton...

..why this man grew to be the tallest in history...

..and why this man can survive underwater for nine minutes

without taking a single breath.

All of these cases are bringing astonishing new insights into how

the body's built and how it works, and the first few cases we'll look

at involve some of the most vital systems that keep us alive.

HIP-HOP MUSIC PLAYS

Seven-year-old Virsaviya loves to pull shapes on the dance floor.

But Virsaviya was born extraordinary.

This is my heart.

I'm the only one that has this.

Virsaviya was born with a condition called Pentalogy of Cantrell that

only occurs in just five per million,

and what it means is that Virsaviya

was born with her heart not inside

the ribcage where it would be protected,

but on the outside, just under the skin.

When I'm getting dressed I put soft clothes on to not hurt my heart and

I just walk around, I jump, I fly.

I run. Well, I'm not supposed to run,

but I love running!

When Virsaviya was born in Novorossiysk in Russia,

doctors warned her mother, Dari, to prepare for the worst.

Doctors told me that Virsaviya have really rare condition,

but they said she won't survive.

When I saw first time how her heart was beating,

of course to me it was something

special. It meant that Virsaviya is

alive and she can breathe and she can live.

Dari moved all the way from Russia to America and her hope in doing

that was that her daughter would be

able to have an operation to put things

back where they should be.

But unfortunately and very disappointingly for Dari,

she was told that Virsaviya just

wasn't strong enough because of problems

with her blood pressure.

We came from Russia to United States.

Doctors check her and they said they cannot help her.

I was really upset about that,

because they kept telling me she will die soon.

It's not easy for Virsaviya to live with heart on the outside because

it's really fragile and she has to be careful.

Of course, she can fall and it can be really, really dangerous.

She can die from that.

When you first see Virsaviya,

what you instantly want to know is how is this possible,

how has her heart formed on the outside of her ribcage?

Well, until recently,

it was a complete mystery, and then the first vital clue came from a

scientist working in a completely different field altogether.

Dr Bob Edelstein is a molecular biologist.

He spent years studying a protein called myosin,

a substance that's crucial to our growth and development from the

earliest days as an embryo in the womb.

Myosin is essentially present in every single cell of the body.

It is able to change the shape of the cell.

It's able to allow the cells to move.

In fact, plays a very important role in cell division.

Myosin has lots of functions within the body,

but one of them is involved in embryonic development.

Myosin enables cells to migrate to

and end up in the positions where they need to be.

To learn more about what myosin does,

Edelstein's team did an experiment in mice where they altered a gene to

stop it being produced in the mouse embryo.

The results were completely unexpected.

Without myosin, the mouse's body plan had gone dramatically wrong.

When we made that mutation we found that the mouse was born with its

heart outside the body.

This was quite extraordinary!

We'd never seen anything like this before.

But purely by chance,

there was someone in the room who had seen this before,

and knew exactly what Dr Edelstein was looking at.

At the time, there was a paediatric cardiologist

who was standing right behind me and said,

"Oh, I know what that is. That's Pentalogy of Cantrell."

I found it very exciting.

It raised the opportunity for the first time to actually maybe try to

do something for people who are ill.

Although the gene that's involved in the malformation in mice may not be

the only one involved in human development,

it has provided Dr Edelstein with an important clue.

Now the team are studying the human genes that make myosin and other key

proteins known to be involved in

laying down the body plan in an embryo.

This is a network of genes which are making proteins that are interacting

with each other and that interaction has to occur at the proper time and

in a proper way in order for the

heart to be placed properly inside of the body.

And that secret is what we're trying to uncover.

Doctor Edelstein is now searching

exhaustively through the DNA of people

with Pentalogy of Cantrell to try

and identify what gene, or what series of genes,

might be a problem.

To do that, he needs saliva samples from people like Virsaviya and their

-relatives.

-Oh, my saliva is pink!

Cool beans!

It was quite clear to me that Virsaviya was very enthusiastic.

I also got the impression she was a fighter and that she really wanted

to see this through and we don't

know that we'll be able to deliver a

cure in the immediate future by any means,

but what we would be able to tell is the likelihood of their next child

having a similar kind of syndrome.

As Virsaviya grows older and stronger,

it may yet be possible to perform surgery on her heart.

And work like Doctor Edelstein's brings hope that by the time she's

old enough to have children of her own,

science will have found new

therapies to treat or even prevent the condition.

When I grow up, I want to be an artist. I want to be a pastor.

I want to be a ballerina.

I want to make movies.

I'm not sure if doctors believe in miracles, but I definitely do.

She's a miracle!

BBC channel, take 11!

What's so amazing about this story of the heart on the outside is

it makes us stop and realise that

we're not just this shape automatically.

In fact, there are a series of

really complex processes that make us this way.

Now, if you peel back the human skin and have a look underneath,

what you see is this network of

bone, muscle, organs, vessels and nerves.

Central to it all is our heart and with it, our lungs and the muscles

around them that we use to breathe.

All of them work together as a finely tuned life-support system,

designed to keep our brains supplied with oxygen round the clock.

If that supply fails, most of us would suffer from irreversible brain

damage within three minutes and die within five.

But there are some people who can survive for much longer and that's

because their bodies can do something amazing that scientists

have only recently discovered.

This is Veljano Zanki, he's broken world records in free diving...

..a sport that involves diving to astonishing depths without any oxygen.

Most of us would be gasping for air after 30 seconds or so,

but Veljano has held his breath underwater for over nine minutes.

It's no accident Veljano has come to excel in this sport.

Here on the Croatian island of Vis where he grew up,

there's a tradition of diving to catch fish with spears.

Nobody wears a scuba tank.

The only oxygen they have onboard is the last breath in their lungs.

It was this that led Veljano to take up free diving as a sport.

He's now one of the best in the world.

These impressive feats are possible partly thanks to a reflex that we

humans share with marine mammals like whales and dolphins.

It's called the mammalian diving response.

As soon as we dive into cold water our heart rate slows,

blood vessels narrow and blood flow is diverted away from the surface

inwards to our brain,

heart and muscles to preserve energy and precious oxygen.

But there's one thing the mammalian diving response can't explain.

Our brain needs a constant supply of fresh oxygen to survive.

So how can divers like Veljano go for so long without oxygen?

To find out, scientists have been studying what happens in their

bodies when they hold their breath for a long time and

they've made an exciting discovery.

This is Zeljko Dujic, a professor of physiology

at the University of Split.

Physiology of the breath hold diving is really taking physiology to extremes.

We can compare breath hold divers to somebody who is at Mount Everest peak.

We found out in our laboratory studies very similar values.

The level of oxygen is very, very low.

By studying free divers, Professor Dujic has helped uncover

why they can hold their breath for so long.

He's observed that when they begin to run out of oxygen, the muscles

that control breathing,

the intercostal muscles between the ribs and the diaphragm below,

go into a rhythmic spasm.

They are usually initially tiny, small, and then at the end, they're

becoming more frequent and stronger and stronger.

That is part of their survival mechanism.

This is the body's last ditch attempt to push blood to the brain

and keep it supplied with oxygen.

It's an automatic response, only seen in extreme circumstances.

The purpose is to increase the blood flow to the brain,

to get more blood and more fresh oxygen to the brain cells and

protect the brain, that no brain damage has occurred at the end of

the breath hold.

This crucial reflex finally explains why free drivers can push their

bodies beyond the normal limits of survival.

And Professor Dujic believes it could have benefits in medicine.

He's trying to find a way of simulating this emergency response

to help prevent brain damage after cardiac arrest.

They're, for sure, extraordinary people and next few decades we'll

continue working with them, hopefully we'll help not only breath

hold divers per se but general population and millions of patients everywhere.

The story of the free divers makes us realise just how robust and

resilient we are.

And if there's one thing that gives us this strength,

it's this, our bone.

And this is the next vital part of our body I'm going to look at.

Our skeleton is what gives us our recognisable human shape.

The whole architecture of our body.

We tend to think of it as fixed and unchanging,

but the reality's quite different.

We're constantly growing and repairing bone, in fact,

we form a whole new skeleton every ten years.

And one of the most fascinating cases I've seen is where this

delicate balance has been disturbed.

Two roads diverged in a wood and I took the one less travelled by...

..and that has made all the difference.

Lines from her favourite poem reflect the extraordinary life of

Jeannie Peeper.

My body has grown an extra skeleton.

Jeannie has a condition that causes her body to grow new bone on top of

her skeleton.

She was a beautiful child, beautiful child.

She liked to jump rope, she liked to play football.

Anything that she wanted to do, she did.

She did not have any hold backs.

My mom realised I was different from her other children.

My mouth did not open as wide and it wasn't until I was about

three-months-old that I started having swellings on the back of my head.

Worried by this strange collection of symptoms in her bones and joints,

Jeanie's parents took her to see bone specialists.

She was about five, five-years-old when they told us that

she would not live to be a teenager.

My husband and I talked it over and we didn't know what to do about it.

Excuse me.

Jeanie suffers from an incredibly rare disorder that only affects

one in two million people.

It's called Fibrodysplasia ossificans progressiva, or FOP.

I didn't know that I had a condition until I was about eight.

I was in fourth grade and I remember it distinctly.

I woke up one morning and I was unable to move my left wrist.

Jeanie's body grows new bone in places where there should be soft

tissue, like muscle.

The slightest knock or bump is a danger.

Where most of us would bruise and then heal,

Jeanie's body starts to make new bone on top of her existing bone

and the reason this causes such a problem is because of the unique

properties of bone itself.

Two of the components that make bone so remarkable

are calcium salts and protein.

To understand what they both do,

I'm going to take first one away and then the other.

This is a chicken bone.

It looks hard, it feels strong...

..but look at this.

The reason why it smashes like that is because I've burned away one of

the key components of bone in this jar of bleach, here,

and what's been left is the calcium salts, which are hard and brittle.

Now, here I've got another bone and this one's been sitting in acid for

seven days, which has dissolved all those calcium salts away.

And look at this one.

It's really bendy and flexible and that's because all that's left in

this one is protein.

Now, you can see how if your bone was like this,

there'd be absolutely no way it would be able to support your weight.

You just wouldn't be able to stand up.

Real living bone is a combination of protein and calcium salts,

making a material that's a bit like reinforced concrete.

Hard, but flexible.

Properties that are useful in the right place,

but as they appeared at random in Jeanie,

they caused her joints to lock and her entire body to become more rigid.

At precisely this juncture where you might expect a normal person

would've shut down their options and just given up,

Jeanie decided that she wanted to really do something about her

situation and her reaction to the difficulties she was presented with,

was to reach out and form a community with other people with the same condition as her.

And what they all desperately wanted to find out was why their bodies

were growing a second skeleton and was there a cure?

What they needed was someone with the expertise to take up their cause

and find the answers.

Doctor Fred Kaplan is an orthopaedic surgeon.

Hi, Joey. How are you?

Good to see you.

As a young doctor he'd come across FOP and the condition intrigued him.

FOP was the worst, the most catastrophic condition

I'd ever encountered during my entire medical school training,

residency training and, er, I couldn't do anything about it.

This just looks like a single nucleotide substitution.

It's in the coding region, so...

Uncovering the mysteries of this condition to try and find its cause

has become his life's work.

Harry Eastlack was a patient who had FOP

and willed his body to medicine.

I often go to the museum to see Harry's skeleton, to observe it,

and each time I go I learn something new.

To discover what caused FOP,

Doctor Kaplan needed to study as many people with the rare condition

as he could find.

Jeannie Peeper's support group gave him a unique opportunity.

Every single patient we saw, they had a malformed toe, and interestingly,

the great toe is the last part of the skeleton to form in the embryo.

It's as if the body gets to the end of forming a skeleton and doesn't

form that last part properly

and then decides to form a second skeleton.

Can you bend forward for me, Joe?

Blood samples showed that the FOP patients all had too much of a

particular protein involved in making bone.

The production of this protein is controlled by our genes,

so it seemed likely a faulty gene was causing the problem.

Because singing helps expand the lungs and it actually helps...

Dr Kaplan knew that there was a genetic mutation most likely behind

this incredibly rare condition

and he was leaving no stone unturned.

Searching the literature, he came across a paper

identifying a gene that was causing a similar bone

condition in chickens.

And he was convinced the two must be connected.

So he looked at the DNA of his patients to see if they had the same faulty gene.

It's the kind of eureka moment that scientists hope for

but rarely happens.

But this time, Dr Kaplan found exactly what he was looking for -

the same error in the genes of every one of his patients,

a single spelling mistake in their entire DNA code.

One letter out of six billion.

That's not one needle in one haystack,

that's one needle in six billion haystacks.

It was an amazing finding and it changed everything.

One of the first people I called with the news was Jeannie.

I was elated.

I couldn't believe it.

And I told him it was truly the greatest gift

of my life to have the gene discovered in my lifetime.

I think she was crying on the phone.

First it was a stunned silence

and then, um...

er, almost disbelief.

Without Jeannie's help studying this condition,

even embarking upon studying this condition would have been almost impossible.

One could not have a better partner in this work than Jeannie.

Here is the case of a woman who has just single-handedly pushed things

forward because of her own very difficult situation,

but also when you see a doctor like Dr Kaplan,

you can see that he is a man who single-mindedly

just wouldn't let this drop

and between this patient and this doctor the most extraordinary

amount of progress has been made in a very difficult disease

in a very short time.

There is no question in my mind that all the ingredients are there

eventually for a cure.

I don't know when that will come

but it can't come a minute too soon.

Dr Kaplan is convinced that curing FOP will only be the beginning,

that this work will ultimately help develop treatments for common bone

problems such as fractures and osteoporosis.

We often think that common diseases will help us understand rare ones.

Essentially, it's the other way round.

Rare diseases help us understand common ones.

The key to the closet is the key to the kingdom.

Jeannie's case reminds us that the skeleton is a finely balanced

piece of natural engineering.

It protects the vital organs beneath it and it also provides a scaffold

on which are the muscles and other soft tissues that enable us to move,

and then just under the skin there is a layer of fat that cushions

and insulates our body.

Now, fat often gets a really bad name,

but actually if it is absent from our bodies,

the effect can be really dramatic,

as our next extraordinary case shows.

Professional cyclists are usually very lean.

But Tom takes this to extremes.

I'm Tom Staniford.

I'm one of eight people worldwide with a very rare condition

that means I don't store fat normally.

Tom's rare condition is MDP syndrome.

One of its main features is lipodystrophy,

which means his body physically can't store fat under his skin

like the rest of us do.

And if that sounds like a blessing, it isn't.

We all depend on fat for more than we realise.

Without bending your knee, please

That's it.

People have a tendency to think that having no body fat as a cyclist must

be great and it would be a tremendous advantage,

but the reality is that it's a big disadvantage.

-Are you happy with that?

-Yeah.

If I come off, the risk of injury is higher.

It's harder to get comfortable in cold weather.

So because I have no body fat around the joints,

my muscles are all naturally tight

and I have reduced flexibility across all my joints.

In an age where people are obsessed with losing weight and being thin,

it might seem as if what Tom has is something that people might envy,

but in fact, the absolute opposite is true.

OK, what can I get for you?

Could I please have a flat white?

And let's have a look at the menu.

Instead of hitting the cake,

Tom has to be particularly careful with his diet.

I think I'd like to go for the bubble and squeak, please, Grace.

OK.

From around 12 years old and onwards,

I started to notice that my energy levels were really fluctuating.

It turns out that I am actually type two diabetic,

which was a big shock because typically people

with type two diabetes are more towards the obese side of things.

As you can see, I'm not really obese.

Tom's body is a mystery.

On the one hand, he's not able to store fat the way the rest of us do,

which makes him incredibly thin,

in fact, medically underweight, and yet on the other hand,

he suffers from type two diabetes,

which is something we associate with people who are overweight.

Tom needed someone who could solve this conundrum.

Professor Andrew Hattersley

is an expert in diabetes at the University of Exeter.

When he first met Tom, he was convinced the clue

to his strange condition must lie in his genes.

The way I like to think of this is that Tom, like all of us,

has three billion bits of genetic information.

But just one of those was wrong

in order to give him all these problems.

So it was like going into a library and trying to find a misspelt word

in one of those books.

And the problem was, if we did come to a book and open it and find there

is a spelling mistake there,

we couldn't be sure that that was the cause of Tom's problems.

As soon as we found another patient with the exactly the same spelling

mistake, then that would really make the diagnosis.

We needed that second case if we were going to make progress.

But Professor Hattersley couldn't find another case like Tom's.

It seemed he was unique.

And then a chance meeting changed everything.

It was a visiting doctor from India who told us that she had got a

patient and there was this remarkable thing that we had

this young man about the same age as Tom, who had exactly the same

physical appearance, who had lipodystrophy.

So it was quite odd,

looking at almost a mirror image of myself in an entirely different life

on the other side of the world.

What this meant was that we now had a second case.

Now, Professor Hattersley could compare Tom's genes

with the Indian patient's and finally he made a breakthrough.

He identified a mutation in a gene that was common to both men.

Now suddenly we could understand why Tom had got diabetes,

why Tom had got the other things as well,

and we had a test that allowed us to pick out this syndrome

with all the other features.

Professor Hattersley had found the cause of Tom's condition.

And to see exactly how it affects the body,

he performed an MRI scan on Tom and compared it to someone

who stored fat normally.

What we can see in the person who doesn't have lipodystrophy,

is round the edge of the body,

there is a layer of fat and if you look within the tummy itself,

there is very little fat shown in the bright white.

And then if we look at Tom's picture, and this is striking,

that round the edge there really is no fat,

but within the tummy we can see great accumulations of fat,

so this is absolutely fat in the wrong place.

What this means is that even though he can't store fat under his skin,

he stores abnormally high levels of fat around his organs and it's

associated with type two diabetes, and it's not a healthy situation.

And then if you remember the advice I gave you early on, Tom.

Avoid the takeaways.

The revelation that Tom does have fat in his body after all,

just in all the wrong places, has changed his life.

One thing that Tom did brilliantly was to increase his activity.

And as a national standard cyclist with all the training that involved,

that helped as well as the diet to keep the fat away

from the wrong places.

And with those two measures alone,

he has been able to almost remove the need to take any medication,

and he has significantly improved the level of abdominal fat that he has.

Understanding Tom's condition and how he's managed to live with it

offers hope for the more than four million people

with type two diabetes across Britain.

Half the people with type two diabetes that I see are not obese,

it's just that they are too fat for their storage.

It has really helped me to see Tom,

who is about the most extreme case of that that you could ever find

because by seeing that you really can understand the much more general

idea of what's the problem in type two diabetes.

All the cases we've looked at so far have shown that there's a delicate

balance which is required for the processes that build

the vital organs and structures of our bodies.

But how does the body know what form to take

and what direction to grow in?

Well, the answer is one of the unsung heroes of the human body.

It's known as the endocrine, or hormone system,

and as with so many things in medicine,

one of the best ways to understand how the endocrine system works

is to look what happens when some part of it goes wrong.

The tallest man ever known was Robert Wadlow from Alton, Illinois.

By the time he was nine, he was a full head and shoulders taller

than his father and could carry him up the stairs.

But this wasn't just a case of a boy growing a bit taller than his friends.

In fact, Robert had an enlarged pituitary gland

and it was pushing abnormally high levels of growth hormone

to his body, forcing him to grow at a colossal rate.

And by the time he died at the age of 22,

he was eight foot 11 inches tall and still growing.

As Robert Wadlow's case shows,

the endocrine system plays a crucial role in how our body's built.

And it's made up of several different glands.

Here we've got the adrenal glands

and up a bit higher here we've got the thyroid gland

and we've got the pituitary gland

and this is like a master control system,

so all of these glands send different hormones around the body

at different times, and by doing that,

the system controls our growth,

our development, our sleep and even our mood.

And to appreciate the power these hormones have on our bodies,

our next case shows how dramatically the effect is

when the balance is even slightly disturbed.

I'm a body confidence activist...

a model...

..and I'm a fabulous bearded lady.

Right.

My name is Harnaam Kaur and I can grow a beard.

When you see Harnaam Kaur, it's not just her amazing beard that strikes you.

It's also her confidence.

But to get here has been a long and challenging journey.

So your whole body goes round and you're looking over your shoulder.

I developed facial hair at the age of ten years old.

I was bullied horrendously.

It was absolutely horrific.

I like the natural one.

Harnaam has a condition called polycystic ovary syndrome or PCOS,

an imbalance in the hormones that control her reproductive system.

In most women, the ovaries produce just the right amounts of three

different hormones - oestrogen, progesterone, and testosterone,

a hormone found in high levels in men.

But Harnaam's ovaries produce too much testosterone,

and this is what triggers excess hair to grow on her face.

When it first appeared, she tried desperately to get rid of it.

I removed my facial hair in many different ways.

I used to thread, wax, shave, bleach.

I even used hair removal creams as well.

But nothing Harnaam did stopped the hair from growing back.

I remember sitting on my bed absolutely ready to end it all.

I was just sick and tired. I had the worst day in school.

And I thought, well, today is the day I just want to go.

And I don't know how it happened but

I had a thought in my head.

I thought, well, if the bullies are allowed to live,

why am I trying to end my life when I have done nothing wrong?

Harnaam made a decision that would change her life.

To accept that her body was different and grow a beard.

The whole school saw me and they saw what I was and who I was and I

thought, do you know? If you want to live like this,

you have to keep on going at it.

And once you stick to something, you've got to be strong.

If you're different, you have to be strong.

Although Harnaam's is an extreme case, around the world,

between 5% and 10% of women of reproductive age have PCOS.

So why does it happen and why does it cause symptoms

that are so challenging to live with?

Stephen Franks is Professor of Reproductive Endocrinology

at Imperial College London.

He's been investigating the hormones involved in this

condition and the effects of testosterone, in particular.

The testosterone levels in women with polycystic ovary syndrome

are typically either slightly raised

or actually still within the upper limits of the normal range,

so they're not screamingly high and nowhere near the levels

in men, but high enough to cause the problems that we see

with unwanted hair.

Professor Franks and his team wondered if the root cause

of these hormone imbalances might be genetic.

They're now part of a worldwide study analysing the genes of thousands of women.

The findings so far do show up some genes that we would expect

to be involved, but a lot of others that we didn't expect at all,

and that's the intriguing thing.

What do they mean, we're asking ourselves,

and I think that's what's going to provide us with further insights

into what causes the syndrome.

Professor Franks believes that identifying the genes that are causing the

hormone imbalance will help tailor new treatments to individual women.

We hope that the genetic studies will lead to better methods

of diagnosis and better methods of treatment.

It's a complex disorder, so I don't think there'll be one cure.

Personalised medicine, if you like.

I hope in the future there is a lot more answers

to why polycystic ovaries happen in a woman's body,

how to overcome it and maybe even a final cure.

Just one hand up.

Harnaam's case really brings home the vital role hormones play

in controlling our body plan.

My beard has given me so much strength.

It's given me a sense of identity, a sense of self-worth.

She is my lady beard. I've given her a persona.

She's going to be ten years old next year

and I'm going to celebrate her so much.

But, yeah, she's something that I absolutely love and adore.

The human body is a complex network of systems, all working together,

and in our final few cases,

we're going to look at the amazing organ that coordinates them all.

The most crucial part of our whole body plan.

The brain.

It's the command and control centre of the whole body,

keeping every part of the plan working.

And there's a fascinating case that shows us just how strongly wired

into our brains that fundamental plan is.

Bryan Wagner has a condition that's difficult for most of us to imagine.

He can feel pain in a limb that's no longer there.

Something that shouldn't be physically possible.

On December 17 2007, I was serving in Baghdad, Iraq,

and we were out on a mission that day and during the mission

we got blown up by a very large IED, or improvised explosive device.

Bryan was evacuated back to the US and had to have surgery

to amputate his right leg.

But strangely, he continued to experience pain

as if his missing limb was still there.

It is a condition called phantom limb.

It feels like you're getting stabbed in the arch of your foot

with a giant nail or

like your foot is in a vice

and someone's cranking down as hard as they can or your

foot's on fire and there's nothing you can do to save it.

Normally, we experience the sensation of pain

when the nerves in the part of the body that's been hurt

or damaged send pain signals to the brain.

But after an amputation, the nerves have gone,

along with the rest of the limb.

So how is it possible to feel pain in a limb that isn't there?

One scientist has made it his mission to understand this condition

and find a way to stop the pain.

I am V S Ramachandran and I study the human brain using mirrors.

Professor V S Ramachandran is a neuroscientist

at the University of California, San Diego.

He's spent years investigating what might cause these strange sensations.

His work has challenged long-held ideas of how the brain works.

The original dogma when I was a student was the notion

that connections in the brain are laid down

in early infancy or even in foetal life and once they are formed

there's nothing you can do to change them.

Connections in the adult brain are fixed and non-malleable.

Professor Ramachandran questioned whether the brain

really was this rigid.

He wondered whether a change to the body as drastic as losing a limb

might also cause changes in the brain.

Other neuroscientists might have used cutting edge technology

to test this idea, but instead, Ramachandran used a cotton bud.

The first patient I saw was a patient named Victor

and he had a vivid phantom left arm

and I tested him with a Q-tip

touching different parts of his body.

He said, "You are touching my chest,

"you are touching my left chest,

"my left shoulder, my right elbow."

Then when I came to the left side of his face and I touched him,

he said, "Oh, my God, you're touching my phantom thumb."

When Victor's face was touched,

he could feel his phantom hand

and Ramachandran thought he knew why.

After the amputation,

Victor's brain had stopped receiving signals from his left arm.

Now it was trying to restore those signals by making new connections

with other parts of his body.

His brain had started to rewire itself.

These experiments showed for the first time that there is

a tremendous amount of malleability in the adult brain.

This rewiring of the brain was restoring a sense of touch

in the lost limb.

But there was one thing it couldn't get over.

The limb is not actually there.

Even if the brain could trick you into feeling it,

your eyes would never see the phantom limb.

Ramachandran wondered if this conflict between touch and sight

might be a trigger for the pain amputees were experiencing.

Every time the brain sends a command, it's getting a discrepancy in visual feedback,

saying that it's not moving

and the discrepancy itself is partly experienced as pain.

Ramachandran had an idea that if patients could see a limb

where their brain was telling them they could feel one,

this might reduce the confusion and the pain.

Now he needed a way to test his theory.

So I said, let's use virtual reality and then I realised

it's going to cost hundreds of thousands of dollars,

but then I hit on a technique of using a 2 mirror.

The idea was that the patient would look at the reflection

of their intact limb in the mirror

to trick their brain into thinking they could see their

missing limb once again.

Professor Ramachandran called it mirror therapy.

I remember my first patient, he chuckled, and he said, "My phantom is moving again."

And I said, "Does it hurt or help?"

He said, "On the contrary it helps me. It alleviates the phantom pain."

Since the early success of this simple technique,

thousands of amputees all over the world have benefited

from mirror therapy.

One of them is Bryan Wagner,

and he's about to meet Professor Ramachandran for the first time.

I am absolutely stoked to meet the professor that came up with this idea.

The guy who through all of his medical training

was sitting in a room one day and was like, "Hey, let's use a mirror."

That just blows my mind.

Good morning, sir.

After months of excruciating pain in his phantom limb,

Bryan first tried mirror therapy with a physiotherapist

who had heard of Ramachandran's work.

It involved placing a mirror to make it look as though Bryan still had

both his legs intact.

And asking him to think about moving them.

I was thinking, "OK, let's just run with this and see where it goes."

She said, "I want you to move your real foot and then move

"your phantom foot." So I moved my ankle up and down,

I wiggled my toes, in and out,

and I would do this for about 20 minutes, twice a day,

five days a week.

And I started noticing the pain decreasing in time and intensity

about three weeks into actually doing this study.

Examining Bryan for the first time,

Ramachandran explains why his pain has reduced.

So you look in the mirror, what you see is your brain sends a command to

the phantom, the phantom has been resurrected optically using the mirror.

It's not really there, obviously.

But it looks like it's following your commands again,

and thereby alleviate the pain.

After I ended mirror therapy,

my pain level went from eight to nine out of ten

to down to like two to three out of ten.

I don't think I would be where I am if he didn't have an

idea to stick a mirror between my legs...

..and move a fake foot around.

Professor Ramachandran's mirror therapy has since been used

successfully on patients with stroke and arthritis.

But perhaps his greatest contribution has been

to transform the way we think about the brain.

Thanks to Ramachandran's research and the work of many other scientists,

we now understand the brain isn't fixed and rigid from the time

we reach adulthood.

It continues to change and adapt throughout our lives.

But there are some events so catastrophic,

such as a fracture to the spine,

that this normal process of adaptation simply can't take place.

And it's in one such case that I've witnessed one of the most amazing

innovations in modern medicine.

I was a freshman in college.

I was majoring in business.

I really enjoyed playing lacrosse, doing hiking with friends,

playing golf and kind of just being your average college student.

Ian was a young man with everything going for him.

Suddenly, his life completely changed.

I was on vacation with a few friends.

I was out in the ocean.

I dove into a wave and it pushed me down into a sand bar

that I didn't see there so it wasn't as deep as I thought it would be.

I instantly knew something was wrong once I hit my head

and I couldn't get up from the water.

What happened to Ian during that accident was that he broke his neck.

And in that one moment,

he went from being a young man with his entire life ahead of him

to a young man fighting for his life in a hospital bed.

Almost impossible to imagine,

something so devastating.

After I had the surgery to stabilise my spine,

I got the diagnosis from the doctor that I was a quadriplegic.

I would have 99% chance of never walking again.

Most likely not regaining any use of my arms.

I would need to have almost 24-7 care

just to go about my daily life.

With a fracture to the spine and a severe spinal cord injury,

there is a complete loss of communication between the brain

and the rest of the body.

And beyond any other kind of injury,

this has always been thought to be completely unfixable.

But Ian's case is challenging this,

thanks to a new idea that's come out of the blue

and from someone who isn't even a doctor.

Nick Annetta is an electrical engineer.

He and his colleagues have developed a new technology they hope might be

able to reconnect the brain and the body after a spinal injury.

It is called a neural bypass.

So the neural bypass technology can be thought of as

a detour around a traffic accident.

So the traffic can't flow any more because it hits the accident

in the spinal cord,

so we create this detour from the brain around the accident

then down to the muscles so that traffic can flow again.

But this was just a concept developed by engineers in a lab.

To find out if it would work in a person,

Nick joined forces with neurosurgeon Professor Ali Rezai

at the Ohio State University.

Together, they worked out it was possible in theory,

but in practice they would need to find a patient willing to undergo

radical brain surgery.

And I was all for it.

It was something that I was really excited about,

but then came the million-dollar question.

OK, well, can we crack your head open and have brain surgery

that you don't really need?

But you can potentially regain use of your arm

and help really push the research further?

I decided to go ahead and have the surgery.

It was a really special moment in Ian's life when he was given an

opportunity by this very unusual team of electrical engineers and

neurosurgeon, neuroscientists to be their guinea pig.

What the team had planned was truly radical.

They wanted to read the electrical signals from Ian's brain

and use them to give him back the ability to move.

In April 2014, they opened up Ian's skull

and inserted a tiny chip into the area of his brain

responsible for hand movements.

It was an incredibly risky procedure.

This is a major surgery that he had.

It might be kind of routine for the neurosurgeons.

As an engineer, looking at someone's skull opened up,

I was concerned for him, so once we knew that he was doing all right,

then it became this waiting game of when do we get

to connect up with Ian?

It took about a month for Ian to recover from the surgery.

Only then could the engineers plug into the device in Ian's brain

and start trying to read the signals.

We started seeing signals like this.

Now, we had to learn the way Ian's brain was talking

about each different motion,

so we asked Ian to think about a particular motion like closing

his hand and then we would look at the firing pattern

of the neurons for that motion.

And the machine learning algorithm that we run would pick out

these subtly different patterns and be able to recognise

these different motions.

Ian started visiting the university three times a week for training

sessions. He watched hand movements on a computer screen and tried to

imagine performing them in painstaking detail,

while the computer attempted to decipher his thoughts.

So after months and months of him going through this training,

they then came to the day where they wanted to try everything out

and see if it worked.

So a really amazing thing to see,

Ian on that day with the stimulator wrapped around his arm,

each bit attached to different muscles in his arm.

He was asked to try and close his hand.

Good.

When we were able to first see that motion of me just

opening and closing my hand,

based on my thought control, it was extremely exciting.

That was something that I thought I would never be able to do

since my accident.

It was a huge relief for us.

It meant that this was really going to work and we really had something

here, but also very exciting just to see Ian himself do this.

I couldn't think of somebody else that I would want to see

do this more.

Ian has progressed with this technology

from a C5 level where he has some proximal movements

of his shoulder to a C7, C8,

where he has individual movements of his fingers.

Which is remarkable and that has never been shown before.

Doctors are always so cautious in what they want to claim for progress,

but you can see the palpable excitement.

The hope would be that if you can improve the function of somebody

who was expected to have none,

how much more could you do for other people?

How far could this be pushed?

At the moment, this system can only be used in the lab,

but the goal is to make it wireless

so that Ian can use it at home,

providing a permanent link between his brain and his body.

The biggest reason I want to regain use of my hands,

using the bypass system, is so I can live on my own.

Maintaining my independence lets me feel like myself again.

And being able to drive my car or being able to do certain things for

myself and I don't have to rely on other people,

it really makes me feel good about myself and know there's really not

anything holding me back, or any big limitation on my life.

The human body plan is unique within nature

and unique to each one of us

and the most extraordinary people on the planet are those

who are helping to unlock its mysteries.

Next time, I'll reveal how the human body can adapt

to the most extreme environments.

Feels good.

And survive against incredible odds.

Having an entire hemisphere of your brain removed

is a pretty radical thing.

It's a world full of extraordinary people.