Episode 6 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.

Despite all the knowledge and technology we have at our disposal,

medicine is still full of baffling cases.

Cases that are difficult to diagnose, let alone treat or cure.

In this programme, we'll discover...

..why this man can taste words.

How this woman's body attacked her brain.

And how this little boy's rare illness was treated

before he was even born.

I'm going to discover how these remarkable people

are challenging scientific thinking, and, sometimes,

even changing the way we'll treat illness in the future.

And I'm going to start with the astonishing case

of a man who invented a new medical procedure

in order to save his own life.

Tal Golesworthy is an engineer.

He has no medical training.

But when he was told he needed life-changing heart surgery,

he decided to take matters into his own hands.

It was fear that drove me, simple as that.

Tal was born with a condition called Marfan syndrome.

His body is deficient in a protein called fibrillin

which helps hold tissues together.

This had a significant effect on how his body grew.

I was always taller than everyone else. I could always reach

the apples higher up the tree than everyone else.

I could always climb over bigger walls than everyone else.

But Tal's condition also affected his heart and vital blood vessels.

In particular, his aorta,

the artery that carries blood from the heart to the rest of the body.

Tal's aorta was weak

and could expand abnormally.

It meant his artery might rupture at any moment...

..putting his life at risk.

Doctors told Tal his only option was major surgery -

to remove his aorta and the valve that connects it to the heart,

and replace them with a mechanical device.

Essentially, they anaesthetise you,

they open your chest,

they then...

literally, cut out your ascending aorta with your aortic valve.

Stitch in the mechanical valve.

Close you up. Put you on a ward.

After the operation, Tal would face a lifetime of blood-thinning drugs

to reduce the risk of blockage in the mechanical parts.

I really did not want that, so, at that point, I just said,

"I've just got to do something about this."

In his professional life,

Tal was no stranger to grappling with faulty mechanics.

So, he decided to approach the problem

as if it were an engineering project.

My take on this was, "Well, OK, the pipe's bulging a bit

"but everything is still working all right.

"If I can put some sort of support around the outside of the pipe,

"and stop the pipe getting bigger,

"I can stabilise the situation and everything will be fine."

Tal's idea was to make a special sleeve to fit around his aorta,

to reinforce it and stop it expanding dangerously.

In this way, he hoped he wouldn't need drastic surgery to replace it

or a lifetime of medication.

Tal had come up with a clever concept,

but he needed to persuade the medical establishment

that it could work

and find a surgeon willing to perform the operation.

Professor Tom Treasure is a cardiac surgeon

at University College London.

Tal first met him when he was giving a presentation on surgery

for Marfan syndrome.

When he finished, he asked for questions, so I just said,

"Why aren't we imaging, modelling, CAD modelling,

"rapid prototyping and making a perfectly fitting implant?"

And he said, "I don't really understand that,

"why don't we talk about it?" And that's where it all began.

I was struck by the completely, sort of, out-of-the-loop idea -

that it really was a totally different approach.

Professor Treasure agreed to work with Tal on his proposal.

Their first challenge was to create a sleeve that would fit.

You've got to have the shape absolutely perfect,

and it's different for every patient.

They made accurate 3D scans of Tal's heart.

These allowed them to design a lightweight, polyester mesh

to fit perfectly around his aorta

and reinforce the weakened artery.

But there was only one way to find out if it would work.

I was absolutely terrified

because I knew what was coming.

I'd stood in on at least a dozen aortic operations,

so I knew exactly what was coming.

In 2004, Tal became the first person to try out his own invention.

I just think on the day, of course, we were apprehensive,

but we had spent four years in the planning

and we knew exactly what we were going to do,

how it was to be achieved.

So, this was just putting the pieces together.

On the 24th of May, the long-awaited operation took place.

Tal's invention was painstakingly fitted around his own aorta.

I suppose, one might call it a seminal moment in one's life.

It was a very...

It was a very, very big moment.

But only time would reveal if the operation had been a success.

Five months later, a scan of Tal's aorta

showed it working better than ever,

thanks to his ingenious polyester sleeve.

Because this was a soft and pliant mesh

with pores big enough for the body

to grow in and out of microscopically,

this mesh became part of the aorta.

So, the body took it into its own tissues

and made a good strong aorta where there was a weak one before.

Now, 13 years later,

Tal's aorta is still working well and he doesn't need medication.

And since his ground-breaking operation,

others have undergone the same treatment.

The first year, we did one.

The second year, we did two.

The third year, we did three or four.

The fourth year, we did five or six.

Until here we are, 12 years after the first operation,

and we've done 22 this year.

To me, as a surgeon, this is a truly inspiring story

of a patient who refused to accept the status quo,

and whose inventive mind and determination

led to a medical advance that's now saving lives.

As a surgeon, I can't help but be fascinated

by a case that's solved by an ingenious new procedure like Tal's.

But in recent years, a new kind of case altogether

has emerged to become a driving force in medicine.

These are some of the most extraordinary

and mysterious I've uncovered.

Cases where a person's body, indeed their whole life,

is shaped by one tiny change

in a single gene among the 20,000 we all possess.

Nick Sireau isn't a doctor.

But he IS on the brink of a medical breakthrough.

I gave up my job to devote myself to finding a treatment

for my children's ultra-rare genetic disease.

Soon after they were married,

Nick and his wife Sonya had their first child, Julien.

After he was born, we noticed some red in his nappies.

We were quite concerned that might be blood.

So, we got some medical advice.

So, next day, we went to see our GP

who got a whole bunch of tests done at Great Ormond Street Hospital

and it came back with a diagnosis

of an ultra-rare disease called alkaptonuria.

Alkaptonuria, also known as AKU,

is a rare genetic condition

affecting just four people in a million.

An abnormality or mutation in a single gene

causes the build-up in the body of a substance called homogentisic acid.

It turns bones and cartilage black,

as we see in this image of an elbow joint.

With this colour change come harmful effects

that usually emerge when a person is in their 20s or 30s.

Over years, it accumulates.

The cartilage starts to harden

and becomes four times tougher than plastic.

So, it's very damaging and the cartilage wears away

and eventually the bone grinds against the bone,

so the hips start to collapse,

the knees start to have problems,

and the elbows and the shoulders.

But also, the heart valves start to calcify

so people start to develop heart problems.

In 1902, AKU was the very first disease

to be identified as being passed down in families.

Yet, over a hundred years since this discovery,

there was still no effective treatment for it.

So, when his second son, Daniel,

was also born with the condition,

Nick made it his mission to find a treatment

before his sons reached adulthood.

We thought we've got about 20 years

to really develop a treatment, you know?

20 years to develop

a new medical treatment from scratch is a tough ask -

even for the pharmaceutical industry.

And Nick had no medical background.

So, how on earth was he going to achieve his goal

and stop AKU harming his children?

Nick may have lacked medical knowledge,

but his job was running charities,

so one thing he did know was how to raise funds.

At the beginning there was very little funding available for AKU.

In fact, there was none.

Nick joined and became leader of the AKU Society,

a charitable foundation,

and threw himself into raising money for research.

So, I was running half marathons and things, raising funds.

And in 2005, we paid for the autopsy of a patient

who'd donated her body to science.

And this was the first time

there'd ever been an autopsy of a patient.

One promising avenue was a drug called nitisinone.

It was hoped it could stop the formation of homogentisic acid,

the substance that damages bones and turns them black.

But early research had been inconclusive,

much more would be needed.

The man leading research into the condition in the UK

is Professor Lakshminarayan Ranganath,

at the Royal Liverpool Hospital.

He conducted a trial of nitisinone in mice,

funded with the help of Nick Sireau.

By trying nitisinone in the mouse,

we were able to show that it decreases homogentisic acid

in a very similar way by more than 95%.

More importantly, we were able to show that if mice were given

nitisinone from birth, they never got the pigment.

And if mice were given nitisinone after a certain age,

the pigment did not progress.

The results of the mouse trial were extremely promising.

But now, a clinical trial in humans was desperately needed.

We realised we had to do our own clinical trial.

And what was a very promising drug

would end up languishing in obscurity

and patients who'd been very hopeful that they'd have a treatment

would be just devastated.

Nick now gave up his job to devote himself full-time

to raising funds for the research.

To date, he and the AKU Society have amassed over £20 million.

They're now conducting a series of clinical trials

involving patients from across Europe and the Middle East.

So, the data confirms that the two milligram of nitisinone

we're using has decreased the homogentisic acid by 95%.

I'm really pleased to say

that all indications,

after three years of using nitisinone

in the National Treatment Centre,

is that it's slowing down the disease. So, we're really hopeful.

These trials are still ongoing,

but since the initial signs are so promising,

the NHS has given special permission

for the drug to be used as a treatment for AKU.

And the reason that the NHS does this for ultra-rare diseases

is that it realises that it can be very difficult

to put together the body of evidence needed

to get approval for a rare-disease drug.

13 years after he began, Nick's efforts have led

to the country's first experimental treatment being available for AKU.

His eldest son, Julien, is now 16,

making him eligible for nitisinone treatment.

We're going to be going to Liverpool in December

where he will spend four days at the National Treatment Centre.

Julien will have a whole range of tests - of MRI scans

and x-rays and everything. And then, he'll be given access to the drug.

This is a remarkable achievement.

The drive and ingenuity of Nick Sireau,

working with Professor Ranganath and his team,

has pushed medical science to the point where, for the first time,

there will likely be an effective treatment for AKU.

I think it's very special that my dad has...

gone through great lengths to help me and my brother.

I feel proud and very thankful.

As Nick's story shows,

genetic conditions are often extremely difficult to treat.

But they can offer scientists a rare opportunity.

Understanding the unusual cases

where something's gone wrong at the level of our DNA

can help unravel the secrets of how all of our bodies

are working normally.

And that knowledge can be used to discover new treatments

for all of us, as we'll see in our next intriguing case.

My name is Pamela Costa and I'm a professor of psychology,

and clinical psychologist, and I work at Tacoma Community College.

To take Pam's classes,

students must be prepared to endure the cold.

Because she has an extraordinary response to warm temperatures.

I feel like I'm on fire.

Pam has a rare genetic disease

called primary erythromelalgia or EM.

If she gets even slightly too warm,

her body reacts in an extreme way.

The symptoms are pretty much...

on fire, pain, relentless, unremitting,

as if your feet, especially,

your legs, and in my case, my hands and my face,

are in an incinerator 24 hours a day...

..that you cannot escape from

in any way, shape or form.

Even when Pam experiences temperatures

that would be mild to most of us...

..she feels like she's in the middle of fire.

The pain is always there. And so, it's kind of

this in-the-background noise, if you will.

And the daily activity that would exacerbate the pain would be

if it's above 65 degrees.

To live with the condition,

Pam has to be in complete control of her surroundings.

We put in porcelain, the coolest floor possible.

Every room, every piece of clothing, is geared towards one goal,

avoiding heat - even at the coldest times of year.

These are her winter shoes.

I get cold, my feet get cold, my body gets cold,

but I'd rather have the bitter coldness

than the burning, fiery pain.

It's kind of choose one or the other.

Pam's condition is an extreme form

of what is known as neuropathic pain.

This is pain that originates at the extremities of the nervous system,

the hands, arms and feet in particular.

For years, nobody could explain why Pam's body

was having such an extreme reaction

to temperatures that were only mildly warm.

Then, in 2004, a discovery was made

that looked like it might not just be able to provide the answer,

but also potentially be of benefit to the millions

of other people suffering from chronic pain.

My name is Stephen Waxman,

I am a professor of neurology at Yale University

and the Veterans Administration Hospital in West Haven, Connecticut.

Professor Waxman and his team made a ground-breaking discovery

about how we feel pain.

Electrical impulses travel from wherever pain occurs in our body

along our nerve fibres to the brain.

Waxman's research revealed how this process is controlled

by specialised molecules called sodium channels.

The way a sodium channel works - it's like a gate that opens.

So, if you were to touch a nail

or if somebody were to take a match and put it next to your finger,

your peripheral pain-signalling neurons

would sense that noxious stimulus

and the sodium channels would open

and that would cause nerve impulses to be generated

and, in the brain, you would recognise - this hurts,

it's a painful stimulus, and, hopefully,

that would trigger a protective response, withdrawal of the limb.

But Waxman and his team observed that people with EM

had a genetic mutation that caused a malfunction

in one particular type of sodium channel.

What we learned is that the EM mutant channels

cause pain signalling nerve cells to scream - brrrr! -

when they should be whispering - bup, bup, bup...

And so when they should be sending a message saying,

"I'm slightly warm", they're sending a signal saying, "I've been burnt".

To understand how the faulty sodium channels

were amplifying the pain signals,

Professor Waxman needed to study the DNA

of as many sufferers of EM as possible.

His work brought him into contact with Pam Costa and her family

who were involved with the Erythromelalgia Association.

They gave him a grant to continue his research

and also connected him to lots more people with EM.

With access to more patients and, therefore, more DNA,

Professor Waxman and others

eventually discovered more than a dozen different mutations,

all of which can result in EM.

Finally, Professor Waxman had identified

the cause and mechanism of EM.

A set of genetic mutations,

any one of which could cause a malfunction

in one particular type of sodium channel called Nav1.7

and it cast new light on our understanding

of how all of us feel pain.

One thing we know for sure from people with EM is that Nav1.7

is a key participant in the generation of human pain.

Not only in people with EM,

but in people with other neuropathic pain conditions.

Shingles pain, pain from diabetic neuropathy,

pain associated with traumatic nerve injury,

traumatic limb amputation

where the nerves are actually severed.

The hope is that having learned that Nav1.7 plays such a crucial role

in pain, drugs can be developed that inhibit its activity

that will be useful in relieving pain in all of these conditions.

And in this respect,

the first small clinical studies are being done right now

and the hints that are coming from these studies, and they're hints,

is that the approach may well provide a new approach

to treatment of chronic neuropathic pain.

Waxman's work on erythromelalgia may well herald a new era

of painkilling drugs for all of us.

Really nice colonies.

Cancer and mental illness...

And Pam Costa now has reason to be optimistic about the future.

My grand vision and hope for the future

of erythromelalgia is a cure.

I'd be happy for a reduce...

Ideally, in my fantasy, I eradicate the chronic pain

caused by this disease.

My hope would be that children would never have to suffer

from this intractable...

pain ever, ever again.

From Pam's rare condition has come a new understanding

of how all our bodies work.

For diseases that are caused by faulty genes,

the Holy Grail is finding a way

to try and rewrite the genetic code to change the DNA.

At the frontier of this are stem cells.

Now, these cells have yet to become a specific tissue.

They might end up being bone,

blood or brain tissue, but they're not YET.

We were all once a ball of embryonic cells

and from this blank slate,

all the different tissues of the body develop.

We know now that stem cells persist right into adulthood

all over the body.

They're there in the bone marrow,

the brain, the heart, the muscle, the gut, the skin.

In fact, there are lots of these little cells

all over our bodies that don't yet have an identity.

They're one of the most amazing discoveries of modern medicine

and there is one truly extraordinary case that reveals why.

This is the King family.

The youngest member is two-year-old Adam.

He is a boisterous, lively toddler,

but he was born with a rare condition

that can make bones so fragile

that even breathing is dangerous.

When we brought Adam home from the hospital,

it was a hugely different experience for us

in comparison to bringing our other three children home from hospital.

All of Adam's care needs had to be carefully planned and calculated

to ensure that we didn't fracture any bones

while we were doing normal tasks

like dressing him and changing his nappy.

That just felt so strange because when you've had the new baby,

-all you want to do is just hold him.

-Hm.

Oh, sorry...

SHE EXHALES

When Fiona was 18 weeks pregnant,

a routine ultrasound scan revealed something unusual about Adam's legs.

The radiographer discovered that the femurs were too short,

they were about three weeks behind on growth.

It kind of looked like, for all intents and purposes,

like a little lightning bolt

which suggested that there were fractures as he was growing.

Their unborn baby was diagnosed with a rare bone condition

called osteogenesis imperfecta,

also known as brittle bone disease.

The couple were told to expect their baby

to struggle immediately after being born.

We had to prepare for Adam not being able to breathe when he was born,

because, obviously, the brittle bones affect all of the bones,

including the bones of the ribcage,

so we didn't know how functional his ribcage would be.

So, we were, I suppose, the first case,

the option we were presented with was termination.

That wasn't an option for us.

Our next option would be just to continue with the pregnancy

and have it monitored.

The prognosis for David and Fiona's unborn baby looked bleak.

It was clear from the ultrasound scan

that he had a severe form of the disease

with his bones already breaking within the womb.

But then they were given a third option,

an experimental treatment

that might just treat his disease

even before he was born.

Fiona and David were put in contact with Dr Cecilia Gotherstrom

at the Karolinska Institute in Sweden.

She had been investigating a cutting-edge treatment

for brittle bone disease.

People with brittle bone disease,

they have one single difference in a specific gene -

the codes for a protein that builds the bones.

And this protein,

the most common mutation is in a protein called collagen.

Collagen is the substance that gives our bones strength.

Without it, they become extremely brittle.

Highly prone to breaks and fractures.

It's especially important for a growing foetus,

as, without collagen, the skeleton won't form properly.

So, Dr Gotherstrom came up with a bold idea -

to treat the condition while the foetus was still in the womb.

What she wanted to do

was to inject stem cells

into Fiona's womb,

and into the unborn baby.

Stem cells are cells which haven't decided yet

what tissue they're going to become.

And so, the idea is if you give stem cells

in a particular condition,

those undecided cells will know where they're needed

and they will develop into the tissue that they NEED to be.

If we give stem cells before birth,

we think that they would find their way to all tissues,

and stay there and help build better tissues and better bones.

The hope is that the stem cells will control the disease

by growing into bone cells that can produce healthy collagen.

Fiona and David travelled to Sweden for the procedure.

Their baby was sedated inside Fiona's womb.

And the new stem cells injected into his bloodstream.

Fiona and David then faced an agonising wait.

They'd only know how effective the treatment had been

once Adam was born.

The birth required a huge amount of psychological

and emotional preparation.

-It was like preparing for a hurricane you know is coming.

-Mmm.

We were prepared for the fact that when Adam was born

that he may not cry at all,

that he would be brought immediately to be resuscitated.

So, thankfully, when Adam entered the world, he was crying,

and it was fantastic to hear.

Adam's crying was a clear sign that the treatment had been a success.

So, we were expecting Adam to be approximately a 4 lb baby.

So, when he was born, he was 5 lbs 11 oz,

which was astounding. We couldn't believe the chubby cheeks.

But his brittle bones and fractures in the womb

had left their mark on Adam -

particularly in his legs.

The only way I could describe his legs...

His legs were so deformed and so swollen,

they looked like bananas.

They were curved in like this.

But since those early days, Adam's progress has been remarkable.

HE GURGLES

He can do so many things

that we never thought he would be able to do.

With all the activities that he does,

he's actually been able to straighten his own legs a lot.

They're still a bit bowed, aren't they?

But, like, he's so... They're so strong.

In comparison to other children with severe types of OI,

he's doing very well.

I do believe that Adam's remarkable progress

is due to the transplanted stem cells.

Next year, Dr Gotherstrom will begin an ambitious clinical trial

funded by the European Union,

involving 30 babies with brittle bone disease.

The hope is that the technique will open up new possibilities

in treating illness before a baby is born.

He is really hardy.

We have four children, and of all four of our children,

there are varying levels of crazy.

And he is at the most extreme end of crazy!

-He loves the craic, basically!

-Mmm.

Stem-cell research is one of the major new frontiers in medicine.

Unlocking some of the most enduring mysteries of the human body,

and enabling us to treat diseases that we once thought were incurable.

And our next case is one of the most remarkable I've come across.

This is Stephen Storey.

He's about to take a scuba-diving exam.

I've scuba-dived all over the world for 20 years,

and that's been one of my big passions.

But just a few years ago, this would have been impossible.

Stephen, in 2013,

experienced a terrifying moment

where he went from being a highly active, energetic person

to somebody who suddenly completely collapsed.

The word I've used to describe it is I just "melted".

My strength just dissipated and I slumped onto the floor.

That was the moment when I realised something was wrong.

Within three days, Stephen was diagnosed with multiple sclerosis.

It's a condition in which a person's own immune system

can attack their brain or spinal cord,

and it can have many different symptoms.

Patients with MS never know

what part of their function will be struck next.

It can affect both brain and body.

Within nine months of a diagnosis,

I was confined permanently to the wheelchair.

So, I couldn't stand, I couldn't walk.

I was finding it difficult to get out of bed.

Difficult to look after myself.

From being a marathon runner,

within 18 months, paralysed, in hospital, 24-hour care.

Which is a pretty dramatic decline.

Stephen has gone from being confined to a wheelchair

to being an active man who can scuba dive.

But multiple sclerosis is a degenerative and incurable disease.

So, how is this possible?

This is Basil Sharrack,

a consultant neurologist

at the Royal Hallamshire Hospital in Sheffield.

Knowing that MS is caused by a faulty immune system,

Professor Sharrack had a bold idea.

To destroy it completely.

The best way, probably, to treat this condition

is to replace the faulty system with a new one which is unaffected.

His plan was then to replace it

using a method developed to treat certain forms of cancer,

which involve stem cells.

This would be a complex and risky process.

First, Professor Sharrack's team had to collect or harvest

healthy stem cells from Stephen's own blood and bone marrow.

Next, they used a high dose of chemotherapy

to destroy his existing bone marrow -

a part of the body where key cells of the immune system are made.

Finally, they reintroduced the healthy stem cells

into Stephen's body.

We give the healthy stem cells,

which we had already harvested, back into the patient.

And these stem cells will start a fresh new system,

which is healthy and unaffected.

The signs are that if patients are given this treatment,

the stem cells will build a new, healthy immune system.

Just over a week after his treatment,

Stephen began to regain movement he had lost.

Nine days after the treatment,

I could consciously choose to wiggle a toe.

It wasn't a spasm.

It wasn't a...

sort of reaction to something.

I consciously thought to myself to move a toe, and it moved.

At that moment, I could feel my body was starting to recover.

At that moment, it made me realise

that this was going to be an incredible journey.

As the treatment is still being trialled,

Stephen is monitored regularly.

Today, he's meeting Professor Sharrack and Professor Snowden

for the results of his latest scan.

-Hello.

-Good to see you again, Basil. Hello, John. How are you, sir?

-How are you?

-Come, make yourself comfortable.

-Thank you very much.

So, Stephen, let me just show you the scan.

So, I'm going to show you, first,

the scan that you had, initially, before the treatment.

So, on that scan, the MS lesions, they look white in colour.

The areas which are white in colour

are areas of active inflammation,

and there's a lot of them, really affecting the whole of the brain.

So, this is the scan from today.

And we are looking for active lesions, white areas.

-Wow.

-And we see none.

So, this is very pleasing.

Wow. I'm blown away.

That is absolutely phenomenal.

Stem-cell research is in its infancy,

in the sense that it's being tried for all sorts of conditions.

But for MS, it's incredibly exciting.

Stephen's case strongly suggests that taking stem cells,

replacing a faulty immune system with a new one,

can have an incredible effect,

not just in halting the progress of this disease,

but actually reversing it.

Today, Stephen is back in his scuba gear.

Under the critical observation of an instructor...

..he hopes to regain his previous diving credentials.

He's waited over two years for this moment.

-How do you think you got on, mate?

-Wow!

I can't begin to explain how amazing that was.

Good news is... Give me a high five. You've just reactivated.

-Well done, mate.

-Really? Wahey!

-Well done.

Absolutely brilliant, fantastic.

Wow, that means so much, Louise.

-Well done, you did really well there.

-Really? Really?!

-Awesome.

From the condition I was in,

unable to move, to get myself out of bed,

to be fed with a spoon,

taken to the toilet, to now,

literally two years to this month later,

being able to scuba dive again...

It's just joyous.

Every day's an adventure, and today's been one of the best.

Um...

Cycling and swimming and all those things are incredible,

but this is something I've had a passion for for years in my life.

And being able to do it again is just...

transformational.

To me, this story represents

one of the great achievements of modern medicine.

Bringing decades of knowledge

from the fields of cancer and surgery together

with the emerging field of stem cells to treat a disease

long thought to be incurable.

But for all this new knowledge and expertise,

there's one vital part of the body whose mysteries

we've still barely begun to crack.

Even in this age of cutting-edge modern medicine,

there's a huge amount we just still don't understand about the brain.

Thanks to advances in imaging technology,

anatomists have discovered

nearly 100 new brain regions in the last year.

And we know that the brain is made up of 100 billion nerve cells,

or neurons, arranged like wires in a vast telephone exchange.

What we're no nearer to understanding

is how this chemical and electrical system

produces intelligence, consciousness or creativity.

And, often, it's when something completely unexpected

goes wrong with the brain, that we learn something new.

This is James Wannerton.

Today, he's sightseeing in the German city of Bonn...

..something he experiences in a very different way from most of us.

Glucose and white chocolate.

Potato wedges.

Chocolate digestives.

Madeira cake.

It may seem like James is obsessed with food.

Soggy, vinegary chips.

But, in fact, this is how James perceives

the street names he's reading.

I can taste words.

James has a condition called synaesthesia.

This is where one of our senses triggers a sensation in another.

When James sees or hears words,

he experiences a taste.

It's like a little eye dropper of food,

I suppose, would be the best of describing it.

Dink, dink, dink. Constant drip.

Ever since I was young,

I navigated by taste.

I've learnt the city layout,

where I live,

my way to school,

I learnt it all by a sequence of tastes.

Every single word has a signature flavour -

even names -

and that deeply affects his relationships with other people.

My friends' names. They all follow the pattern.

They're all very nice, tasty names.

I've had plenty of friends called Robert.

Tastes of strawberry jam sandwiches, for some peculiar reason.

I would never have a friend called Alan

because it gives me the taste and texture of dried mucus,

would you believe.

There are various forms of synaesthesia.

All of which involve an unusual interaction between the senses.

Some people see colours when they read certain letters or words,

or hear particular sounds.

But James's version,

the ability to taste words,

does seem very bizarre.

Jamie Ward is professor of cognitive neuroscience

at the University of Sussex.

He took MRI scans of James's brain

to find out what could possibly explain his strange sensations.

We took words that have particular flavours for him.

So, we take words that are very intense,

or words that produce flavours that are horrible,

or words that produce flavours that are quite weak and neutral.

When he compared James's brain scans to an ordinary person,

he saw something remarkable.

When you or I hear a word,

a part of the brain called the auditory cortex activates.

And we understand the meaning of that word using the temporal lobes.

But that's not all that happens in James's brain.

Another part that is involved in taste and emotion also activates.

And a third area lights up that's involved in how we process images.

So, there's a lot more activity in James's brain.

This suggests synaesthesia is physical

and rooted in how the brain is wired.

So, not only do they have these unusual experiences,

they actually think differently. They think in images.

They also seem to have better memory.

And this might be that they can use their synaesthesia

to help them to remember.

But it also seems to be the case that their brain is predisposed

to form these better connections,

and hold on to information in a way that other people don't.

As scientists discover more about synaesthesia,

they're beginning to use that knowledge

to help people with sensory impairments.

People like Daniel.

He's blind.

But work being done by Jamie and his team

is allowing him to build up a picture

of the world using a different sense altogether.

So for example, people who don't have vision,

we might be able to express the visual world to them using sounds.

As Daniel moves,

a camera detects the structure and position of nearby objects

in three dimensions.

This information is converted into sounds.

He's going from left to right.

-Now walking towards me.

-HIGH-FREQUENCY TONES

Changes in volume and pitch correspond to how near or far...

Going back. Further away.

..an object is.

Closer again.

Different instruments also indicate colour.

There is a clear distinction between red or green, blue.

DIFFERENT TONES PLAY

So, the first sound I can hear on my left is...

RESONANT TONE

..a deeper cello sound?

And I know that this is associated with a blue colour.

-Then the next one up...

-HIGH-PITCHED TINK

..is a really high-pitched violin sound.

So, that should be a yellow.

To some extent, we can think of blind people training themselves

to be synaesthetes,

so far as they're taking something that is purely auditory,

and they're using visual parts of their brain

to process this auditory stimuli.

The inspiration for this technology comes from people like James

and their amazing ability to combine the senses.

Madeira cake.

It's a major part of my life.

It feels very natural and normal to me.

If I had it taken away, I couldn't remember anything.

Chocolate digestives.

Through cases like James's,

we're learning more about how the different parts of our brain

connect and interact

to give us our understanding of the world around us.

But the brain doesn't always give up its secrets so easily.

In our final, remarkable story,

we'll meet a family whose quest for answers

revealed a new understanding of how our brain works,

what can go wrong with it, and how we can treat it.

My name is Emily Gavigan

and my body attacked my brain.

I was home for winter break,

and I had gone to a coffee shop with some of my friends.

And I was leaving the coffee shop,

and I was very suddenly manic and paranoid

that these trucks were following me.

This paranoid episode wasn't unique.

In the months before,

Emily's parents, Bill and Grace,

had noticed a change in her personality.

She became really just a different person.

We actually thought that possibly she was,

she had gotten into, maybe, drugs.

We took her to a doctor,

and they started to treat her

as though she had a psychiatric illness,

especially because of the paranoia,

the aggressive behaviour.

A psychiatrist prescribed Emily a series of mood-stabilising drugs.

But nothing seemed to help.

She was eventually admitted to a psychiatric hospital.

During that stay in the hospital,

they were leaning toward the diagnosis of schizophrenia.

They told us that she would not be able to work again.

They said that she would not be able to function normally.

But Emily soon started to show symptoms

that just didn't fit with schizophrenia.

My mom and I were headed to the pharmacy to pick up some medication.

We got out of the car to go into the pharmacy, and I couldn't walk.

Emily was rushed to hospital.

Doctors suspected something was causing inflammation in her brain,

and changed her medication.

But she had a severe reaction to the new drugs.

She was in critical condition.

I asked the neurologist to come back into the room to re-examine Emily,

to really look at her.

And Grace asked him if he thought, you know, Emily would die.

He couldn't say that she might not during the night.

Desperate for answers, Bill had been reading everything he could find

that might bring a clue to what was happening to Emily.

And he'd read a report

of a young woman with similar symptoms to Emily,

who was also diagnosed with mental health issues.

But, in fact, something else completely was going on.

Her own immune system was attacking her brain.

So, after they took Emily to the intensive care unit,

I stayed behind and I asked the neurologist to stay behind,

and I handed him the article

that had been written in the New York Post.

And I insisted that he read the article

while he was standing in front of me.

Emily was immediately airlifted

to the hospital of the University of Pennsylvania.

This was where the patient Bill had read about had been diagnosed.

Dr Maria Chen was a neurologist on Emily's team.

When Emily arrived at Penn Medicine,

she was in a critically ill state

as a result of seizures

and a blood clot that she sustained.

The doctors immediately suspected

that Emily had the same condition they'd diagnosed before.

A rare autoimmune condition

called NMDA, receptor antibody encephalitis.

NMDA, receptor antibody encephalitis is a condition

where your body's immune system

generates antibodies that inadvertently target

your body's brain and cause dysfunction.

NMDA receptors are situated in the part of the brain

that's important for learning and memory.

Tests for the condition came back positive.

Emily and her parents finally had a diagnosis.

So, Emily was not thinking correctly

because if this receptor is not engaged and working properly,

you can have paranoid thoughts.

You can have inaccurate memories.

Emily started a new course of treatment

to suppress her immune system and remove the antibodies

that were attacking her brain.

And she began to recover.

I look like...

mess.

-You look like?

-A mess.

No, you don't! I think you look pretty good.

SHE LAUGHS

I had to relearn everything from how to brush my teeth,

how to feed myself,

how to tie my shoes,

that kind of basic stuff

that you don't think about any day.

Thanks to her father's persistence,

Emily eventually received the right treatment and made a full recovery.

But, to me, the end of Emily's story

is just the beginning of a new chapter

in our understanding of how the brain and the body

affect each other, causing symptoms that, even today,

can be difficult to diagnose.

Professor Belinda Lennox

is a psychiatrist at the University of Oxford.

In mental health, in psychiatry,

we diagnose people based on the symptoms that they describe to us.

We have no blood tests. We have no investigations.

We have no diagnostic tools

for the serious mental illness

that I see as part of everyday clinical practice.

Professor Lennox suspects that some people who are thought to have

certain severe mental illnesses

may actually have conditions similar to Emily.

To find out, she and her team

screened more than 200 patients across England.

Almost 10% of them either carried

the antibody against NMDA,

or one similar.

Over the last few years,

we have been treating people with schizophrenia

who have been found to have these antibodies,

with immune therapy,

alongside their standard psychiatric treatment.

In our experience, people do get better.

The results so far are very encouraging.

And Professor Lennox is about to start a trial

that will compare the effects of immunotherapy

against placebo in treating psychosis.

If successful, it could revolutionise

the way doctors approach the diagnosis of conditions

that affect the brain.

Ensuring that more patients get the right treatment and recover.

Like Emily.

Her personality has come back.

She's that same person who was very outgoing, and very loving,

and the person that we had before.

She's just a wonderful person

and we're very, very happy.

Going through this illness has definitely changed me.

It showed me that, sometimes, you do get second chances,

but not to take them for granted.

Emily's story is a powerful reminder

that we're learning new things about the human body all the time.

And throughout this series,

we've encountered people who are helping to drive that progress.

Individuals with superhuman abilities,

others with incredible resilience when their body goes wrong

and the doctors who are unlocking their secrets.

This is truly the frontier of modern medicine, and it's come about

thanks to some of the most extraordinary people on the planet.