Episode 5 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 Jodi Seneca, 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.

There's no time in life more amazing than the nine months we spend

developing inside the womb.

We go from two single cells, a sperm and an egg,

to a fully fledged human being within the space of a year.

It's one of the most incredible transformations in the natural world.

And the slightest mistake can shape our bodies in extraordinary ways.

In this programme we'll discover why this man has super-strong bones,

why this woman has two wombs,

why this girl's arm won't stop growing

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

The tiniest flaw or mutation that occurs when a cell divides,

even in a single gene,

can have the most enormous impact on how our bodies work.

And this is bringing some of the most exciting new discoveries in medicine,

as our first case shows.

Ceniya looks like a pretty normal ten-year-old.

I like to do basketball, tennis, archery,

swimming and dancing and gymnastics.

And this makes her extraordinary.

My name is Ceniya.

I have a sickle cell disease, but I am not sick.

Ceniya has a debilitating disease called sickle cell.

She shouldn't be able to run around like this.

But it looks as though nobody has told Ceniya.

When Ceniya was born, she was a sweetheart.

You know, she was always smiling, always playful.

But shortly after she was born,

Ceniya was diagnosed with sickle cell...

..a blood disease that can lead to pain, strokes and infections.

It can be fatal.

And, as yet, there is no cure.

We were told it was the worst type and, basically,

that she's going to have all these crises,

and going through pain all her life,

and her life expectancy was going to be low.

That moment was just devastating.

Sickle cell disease is an inherited condition that requires inheriting a

faulty gene from your mother and your father.

It's suffered mainly by the African-Caribbean community.

I have family members that have sickle cell disease,

and I've seen the pain, and all of the agony that they go through,

and all the hospital stays.

So I cried a lot.

You know, just knowing my daughter was going to have to go through this.

Ceniya was referred to the Children's Cancer and Blood Disorder Center in Boston.

Her doctor is Matthew Heaney, who specialises in sickle cell disease.

Sickle cell disease is a disease of the red blood cell.

In our body we have trillions of red blood cells.

Red blood cells move through the blood vessels

to mostly deliver oxygen to the rest of our body.

All of our tissues and organs need oxygen.

Red blood cells are full of haemoglobin,

a protein that carries the oxygen, seen here in blue.

Normally, these cells are disc-shaped and flexible.

But sickle cell patients have a faulty version of haemoglobin.

After it's delivered its oxygen to the body it causes a catastrophic change

in the shape of the red blood cells.

The diseased cells form an abnormal sickle shape,

and these little sickles, within the red blood, are rigid,

and they get stuck in the blood vessels,

causing pain and other things like strokes.

But Ceniya is not suffering any of these symptoms.

How you been since I last saw you?

-Good.

-You had any problems?

And it doesn't look like you've been in that emergency room since I last saw you.

No.

Since being diagnosed with sickle cell disease as a baby,

Ceniya's family have been expecting her to fall seriously ill at any moment.

But it hasn't happened.

How can Ceniya have a life-threatening illness

but no symptoms?

Dr Heaney was determined to find out.

So when Ceniya was one year old, he took a blood sample.

And he found out that it contained high levels of a type of haemoglobin

he wasn't expecting to see...

..foetal haemoglobin,

a kind we have when we're still in our mother's womb

and not yet taking in oxygen by breathing.

It's a very special type of haemoglobin, for that environment.

It has a very high affinity for oxygen,

meaning it holds on to oxygen tightly,

and can extract oxygen from the mother's placenta for life in the womb.

The instant we're born, we're suddenly in an environment

with much more oxygen.

It means our blood needs to adapt quickly in the very earliest moments

of life.

And I'm going to show you one of the many reasons why.

Now, obviously, we need oxygen to survive.

But if we have too much of it,

it can cause the formation of highly reactive and damaging molecules.

Now, this is one such highly reactive substance.

It's known as hydrogen peroxide,

and it can cause a huge amount of damage within the body.

Now, if I add some of this substance to water...

..very little happens.

But look what happens when I add it to blood.

Just look at that!

Now, obviously, newborn blood doesn't foam and bubble in that way,

but the principle is the same.

There's an enzyme in the blood called catalase,

and what that's doing right now is neutralising the hydrogen peroxide

in a way that makes it less harmful.

Newborn babies have extra levels of this catalase in their blood,

in the first few days of life,

while they're becoming accustomed to the extra oxygen in the outside world.

As soon as a baby is born, one of the key changes in their blood

is that they switch from foetal to adult haemoglobin,

which adapts to the extra oxygen in the air.

By the time we're a year old,

most of us only have a trace of foetal haemoglobin left.

About 1%.

But Ceniya is different.

At the age of one, she had more than 30%.

And Dr Heaney suspected that this was why she wasn't displaying

any of the symptoms of her disease,

because foetal haemoglobin doesn't form the problematic sickle shape.

Sickle haemoglobin sticks together when it's lost its oxygen.

The foetal haemoglobin doesn't participate in that sticking together.

So the more foetal haemoglobin you have,

it interferes with that interaction,

and allows the cell to stay in a nice disc shape,

and not take up the stiff and unbendable sickle form.

Ceniya's case is highly unusual.

So why is it that most of us switch almost entirely from foetal

to adult haemoglobin at birth but rare individuals like Ceniya don't?

Scientists hope that if they could uncover that secret,

it might lead to a new treatment for sickle cell disease.

Dr Stuart Orkin is a researcher at the Boston Children's Cancer and

Blood Disorders Center.

One of the really central research activities within the entire field

has been to try to understand how it is that we switch

from a foetal haemoglobin to an adult haemoglobin,

which occurs, really, around the time of birth.

Dr Orkin suspected we must have specific genes responsible for the

crucial switch from foetal to adult haemoglobin.

For 30 years, he combed through the genes of families with

and without the disease,

searching for one tiny difference that could lead him to the switch.

Eventually, he found a gene called BCL 11A

that seems to be different in people with sickle cell disease.

It was a major step forward,

but now Dr Orkin desperately needed to find out if this gene really

could be the switch he'd been looking for.

To find out, Dr Orkin did some experiments with mice.

He took a mouse with sickle cell disease

and removed the BCL 11A gene.

What he discovered was remarkable.

This is the image of a blood smear of a mouse with sickle cell disease.

You can see these funny-shaped cells, sickle cells.

Now, we've taken this kind of mouse, and we've removed the gene.

And when we do that,

you can see that the cells now take on the normal appearance.

They are now quite round and uniform.

These mice have normal blood and a normal life span.

So that experiment demonstrates that removing the gene cures sickle cell

disease, at least in this mouse model.

This is an exciting breakthrough.

By removing one gene, scientists have altered the switch.

So the mouse continues to produce more foetal haemoglobin,

which doesn't form sickle cells.

Now there's a new hope of a treatment for sickle cell patients.

The goal would be to be able to have a pill that we could give to an

individual and instead of having 1% foetal haemoglobin,

maybe we'd have 10%.

And I don't dare predict when, and if, that will occur.

But it's a goal that is worthy of research.

If Dr Orkin can harness what he's learned in his research,

tens of thousands of people suffering from sickle cell disease might have,

in their future, the possibility of leading healthy, active lives.

Just like Ceniya.

I hope that soon, like, when I get older, the doctors find my cure,

and they give it to those people, and they, finally, can do what I do.

Ceniya for president, remember I said that.

THEY LAUGH

Ceniya's case shows us one single,

but vital, stage in the unimaginably complex process of how we grow and

develop from one tiny bundle of cells in our mother's womb

to a fully formed human made up of trillions of cells.

The next cases we'll look at reveal

how these cells that our bodies are made up of

can grow in extraordinary ways.

In 2005, Clare Miles gave birth to twins.

But this had been no ordinary pregnancy...

..because Claire has two wombs.

And each baby grew in a separate womb.

Claire was born with a condition called uterus didelphys.

She was completely unaware of it until she was 20,

when she had to have emergency surgery.

I'd had an abscess on my vagina wall, which

had caused a great deal of pain.

And I woke up to discover that I had...

two wombs.

Claire's condition helps us understand

how our bodies are formed in the womb.

Normally, the female foetus starts off with two separate tubes that

eventually fuse to form a single womb.

But in about 3% of babies, this fusing process gets disrupted.

And in some rare cases, a girl is born with two wombs, like Claire.

It's even more rare, and very risky,

to have a pregnancy in both wombs at once.

That's because each uterus can go into labour at a different time.

But on the 8th of June 2005,

Maisie Rose and Noah Henry both arrived safely

by Caesarean section.

It's often in cases like these,

where a person's body grows in an unusual way,

that we can trace back to the beginning of the process,

and uncover the secrets of how our body's built.

In our next case,

we'll meet one girl whose body isn't growing the way most of us do.

Hi, I'm Leah Hardcastle, I'm 14, and I love to ride horses.

Leah has a very unusual condition that affects how her body grows.

She's had this from birth, and really,

it's just where certain areas of Leah's body are growing far quicker

than other parts of her body.

My arm just looked different.

I mean, this arm is absolutely fine.

No problems. And then the left arm, my hand,

it just looked out of proportion.

It turns out Leah is one of very few people

who are suffering from a condition called segmental overgrowth.

And what that means

is that Leah's left arm is growing continually at an abnormal rate.

In 14 years, she's had over 30 operations to reduce the size of her arm.

Each surgery, it will get better for a few months,

and then it might just grow really fast,

or it will grow eventually.

This is a condition that doesn't affect any other part of Leah's body.

Only her left arm keeps growing.

So why does this happen?

The answer could lie in pioneering research being carried out by

scientists in Cambridge.

My name is Robert Semple,

I'm a principal investigator at the University of Cambridge

in metabolic science.

Dr Semple believes Leah's condition has its origins in the very

earliest days of life in the womb,

when an embryo is made up of just a few cells.

We all start out as a fertilised egg,

and in that egg there is a shuffling of the genes from our mother and

father. And it provides the full complement of genes

which are transmitted to all the cells of our body in adult life.

So one cell becomes two cells,

that becomes four cells,

but this all relies on all 20,000 genes being copied accurately.

And if there's a change in a gene which allows a cell to survive,

and which changes the properties of that cell,

then this will appear at this stage,

so this is represented here by yellow.

So we now have a situation where the embryo contains a mixture of normal

cells, with the same genes as the parents, and one abnormal cell.

In Leah's case, the part of her body that has become her left arm had a

mutation in one of the genes that meant that that part of her body has

developed abnormally.

And Dr Semple had a good idea which gene was responsible.

By the time we met Leah we had worked out from studying similar patients

that nearly always the change was in the PIK3CA gene, so therefore,

we focused first on the PIK3CA gene.

PIK3CA is a gene that is involved in controlling growth.

Because Leah has an abnormality at this particular point in her genetics,

what that means is that her cells just don't know when to stop growing.

This reminded Dr Semple of a different illness altogether...

..cancer,

a disease that's also caused by an uncontrolled growth of abnormal cells

in a part of the body.

And this similarity gave him an idea.

We knew that if we could take some of those medicines which were being

used in cancer, it might give us a chance of reducing the growth,

possibly even shrinking down the extra growth in patients like Leah.

Leah has just been involved in an initial trial

of one particular cancer drug,

and has come to Addenbrooke's Hospital in Cambridge.

The machines will come to the top of your head.

And when it's scanning back down is when it's actually scanning you.

OK?

Scientists are scanning Leah's body so they can monitor the mass

of her arm.

The top arm seems to have stayed

roughly the same.

This time there's not much change.

But it's early days for the research,

and this is just one drug among several that Dr Semple intends to

trial in the hope that a cure can be found for patients like Leah

in the future.

She has played a really important part,

and we will be running more studies starting next year,

and in subsequent years,

and we'll make sure we offer her the chance to play her part in those as well.

If these trials really do help, I'd be up for it.

Any time. Because helping anyone else is just my main priority.

Leah's story reveals the key process in our transformation from a bundle

of cells to a fully fledged adult.

As we grow and develop, our cells divide and divide again.

But this process is anything but haphazard.

It needs to happen in a controlled way,

and among the most astonishing cases in the history of medicine is one

where the cells just didn't know when to stop.

Henrietta Lacks has the most extraordinary cells on the planet.

Yet she died more than 60 years ago.

And in her lifetime, there seemed nothing remarkable about her.

Henrietta Lacks came to Baltimore with her husband,

they lived in an area where many African-Americans from the South came.

James Potter is assistant professor of medicine at the Johns Hopkins

University in Baltimore.

She went to a doctor complaining of pain,

and he referred her to Johns Hopkins.

That's when her cervical cancer was discovered.

The doctors found a tumour and took biopsies for testing.

But her cancer had spread, and Henrietta died.

She was just 31 years old.

But the cells from her biopsies were still in the hospital laboratory,

and the lab technicians noticed they were doing something very unusual.

The technicians were the first to really get excited,

when they saw that there were individual cells growing.

They knew this was different from all other attempts

to grow human cells in culture.

Back in the 1950s, scientists were only able to preserve human cells

outside the body for a few days or weeks.

They wanted to use them for vital research into cancer and other diseases.

But often the cells would die before their investigations were complete.

Henrietta's cells were different.

These cells continued to grow.

The researchers were able to grow them in large quantities,

they did not begin to die off or to change their characteristics.

This is a time-lapse of cells taken from Henrietta Lacks's tumour.

They were multiplying at an astonishing rate,

each cell dividing every 20 hours.

And here they are six weeks later, they are still alive,

and thriving in the test tube.

Even if they are in the air or on a benchtop, they still survive,

they were entirely different from any cells isolated previously.

Here were human cells that appeared to be immortal.

Scientists could experiment on them safe in the knowledge

that these cells wouldn't die.

So how is this possible?

Inside our cells our DNA is arranged in structures called chromosomes.

The tips of our chromosomes are called telomeres.

Each time a cell divides, these become shorter.

When they get too short, our cells stop dividing and die.

But in Henrietta Lacks's cells,

researchers found high levels of an enzyme called telomerase.

This rebuilds the telomeres so they don't shorten.

And that's why her cells weren't dying.

Using letters from Henrietta Lacks's name,

scientists called these cells HeLa.

And soon they began to be shipped to laboratories around the world

for research into new treatments and cures.

Having the immortal cell line, the HeLa cells,

had immediate repercussions in medical research.

Almost immediately,

the approach to developing a polio vaccine was available.

And the rapid growth of HeLa cells

allowed for the development of a polio vaccine.

And this was only the beginning.

HeLa cells were used to test the effects of radiation from atomic weapons.

They were sent into space to study weightlessness.

They've also been used to help develop therapies for Parkinson's disease,

Aids, blood disorders

and have played a key role in research into stem cells.

HeLa cells have probably been the most important tool in the last half

of the 20th century for medical research.

The number of lives saved because of HeLa cells is in the millions.

One small difference in the cells of Henrietta Lacks gave them their

unique ability to carry on growing outside of her body

and, in so doing, drive the progress of science.

It's also a fascinating insight into what's going on inside us

all the time.

The fundamental process of cells dividing in a controlled way

is the key to how our bodies grow and develop throughout our lives.

And one of the last parts of the body to develop into its adult form

is the skeleton.

Our bones are far from mature at birth.

Throughout life, a process called ossification,

which means the replacement of cartilage with bone,

passes through the body.

In most of us, this whole process is complete by the time we're about 25.

But there's one group of people in whom this process has gone awry.

And these unusual cases are helping us understand exactly

how this crucial part of our body forms.

At first glance you might notice something a little out of the ordinary about Tim.

I look a bit different, yeah.

And it's because, inside, he hides a pretty amazing secret.

I have super-strong bones.

Tim has a condition that makes his bones super dense -

in fact, 1.5 times denser than granite.

No-one knew about it until Tim was nearly two years old.

Initially, I had facial paralysis.

And one half of my face, my dad mentioned one day,

I got in the car, and I was smiling,

but I was only smiling with half of my face.

And they thought I was playing a prank.

But Tim's facial paralysis didn't go away.

Doctors performed some X-rays and found that Tim had an extremely rare

condition, shared by just 50 people worldwide.

I have sclerosteosis.

It's a condition characterised by excessive bone formation.

While sclerosteosis, or strong bones, might sound like a good thing,

the reality is this condition put Tim's life in danger.

As a child, his skull started to grow so thickly

it put pressure on his cranial nerves and brain.

If you try to alleviate that, then you will very likely die.

They really have to cut open the skull,

remove part of the bone, they hollow it out,

then put it back.

And immediately, you've got some more space for the brain.

Doctors could treat Tim to alleviate the problems caused by the excess

of bone, but no-one knew why he was growing extra bone in the first place.

His condition's just so rare

that there hasn't been much research into it.

But then Tim's condition caught the attention of scientists who were

studying a much more common bone disorder,

one that seems like the polar opposite of what's happening to Tim.

Dr Alistair Henry is a structural biologist.

He's part of a team that studies osteoporosis,

a loss of density in bone that leaves it weak and fragile.

So when they came across Tim's condition, they were intrigued.

Sclerosteosis patients, they make normal bone,

but of a much greater density.

So the architecture,

the three-dimensional structure of their bone is normal.

But much more dense.

Dr Henry's team set out to discover what was making the bones of people

like Tim so much denser than normal.

They looked at the genes known to control bone growth,

and discovered a fault in a particular gene called Sost.

This gene makes a protein called sclerostin

which tells our bones when to stop growing.

And it wasn't working in Tim.

People that have the mutation in the Sost gene, the sclerosteosis patients,

never make sclerostin.

Without sclerostin, Tim's body doesn't know when to stop making bone.

So he just keeps on making more.

This knowledge gave Dr Henry and his team an idea for a potential new

way to treat osteoporosis.

When we'd identified that sclerostin was the protein

that controls bone density,

what we wanted to do is neutralise its effect.

We knew that if we did that we would effectively take the brake off the

process of building new bone.

So using this principle, Dr Henry and his team worked for several years

to develop a new drug to treat osteoporosis.

The next stage was to put the drug to the test.

One such opportunity came in an unexpected place.

Liftoff! Space shuttle Atlantis.

In 2010, the Atlantis space shuttle blasted off

with four astronauts on board.

Astronauts can lose up to 30% of their bone strength in just six months

while in space.

And Nasa was keen to explore how to stop that loss.

So they agreed to carry some extra, tiny passengers.

12 mice.

Half were given a version of the new drug,

and after 13 days their bone density had increased,

while the bones of the other mice had weakened.

The drug had worked.

And now, clinical trials involving human patients are under way.

Tim now has some answers about his condition.

And the millions of people suffering from osteoporosis may well have the

promise of an effective new treatment.

This really is amazing, for me it's fantastic news, actually.

It really makes everything that we've gone through, all the surgery,

all the stuff that my parents and everyone went through,

it makes it worthwhile.

Tim's case is helping scientists understand how our skeleton,

the very architecture of our bodies,

continues to grow throughout our adult life.

The growth of cells in adults is mainly to do with maintenance and repair.

But there's one part of the body where this process isn't so

straightforward, where tissue can't just replace itself in the normal way.

This is the nervous system, and the reason is to do with risk.

If nerves just randomly replaced themselves,

parts of the body would lose their connection with the brain,

and this would be catastrophic.

This also explains why spinal and nerve injuries are so hard to treat.

But there is one kind of nerve cell that is capable of regenerating,

as one extraordinary case shows.

Louise Woollam is an award-winning perfume journalist and writer.

But two years ago something happened that profoundly changed her life.

I completely lost my sense of smell.

Louise's sense of smell stopped working after she caught a cold.

Maybe if you breathe in deeply and slowly...

No.

It's something many of us experience and it usually gets back to

normal when the cold clears up.

But not for Louise.

A few days after the cold cleared up, I was at a perfume launch and I

realised that I literally couldn't smell anything.

It was really disconcerting.

And then something unexpected happened.

Louise's sense of smell started returning, but not in the way it should.

Anything that had a smell smelt bad.

It didn't matter whether in real life if it was a good smell

or a bad smell, I literally experienced it

as either a burning smell, or rotting onions, or burning meat.

I thought I was going a bit mad.

It's a condition called parosmia.

Smells that used to be familiar and pleasant

were now bizarre and repulsive.

That's really weird.

The worst thing was that everything that smelled bad

tasted the way that it smelled as well.

It's kind of a chemically... petrol sort of taste to it.

Food was beginning to taste rotten.

I had a bite of a chocolate biscuit and it tasted of, like, burnt leaves.

My mum would cook Sunday lunch and it tasted like

she'd just poured sewage over the top of it.

As Louise was discovering,

our sense of smell plays a vital role in the way we experience and

understand the world around us, one we often take for granted.

A perfume writer losing her sense of smell is actually,

it's quite amusing and I understand...

Sorry.

I understand why people think it's funny...

and most days I think it's quite funny as well because...

..people don't really understand how important smell is

and what an impact it can have on your daily life.

Louise has gone from losing her sense of smell to having it come back

but go completely awry.

She can recognise common odours

but nothing smells the way it should and,

in fact, most things smell horrible.

So clearly something highly unusual is going on

between her nose and her brain.

Normally, the way smell works is that we breathe in molecules

in the air that contain odours.

These are picked up by tiny receptors at the back of our nose,

which are the very ends of our olfactory nerve.

The nerve then transmits signals to the olfactory bulb

and then deeper into the brain,

which gives us our experience of the smell.

It's this process that's been disrupted in Louise.

One person who can help put it right is Chris Kelly.

She lost her sense of smell in the same way as Louise

and since then has spent years researching the condition.

I imagine it a bit like a telephone exchange,

where on the day that you lose your sense of smell,

all the wires are pulled out and just chucked on the floor.

And then in time some of those wires rise up

and sort of start sticking themselves randomly into sockets

and, of course, all the information that you get

is cross-wired and is not...

You're not making the right connections.

It's a question of the brain not being able to interpret the information

available to it because the signals are scrambled.

So Chris made it her mission to unscramble the signals

and retrain her brain to recognise smells again.

Basically, smell training is simple.

You have to engage your brain, it is brain training.

You are building new neural pathways,

and doing that every day exercises a part of your brain.

It's like physiotherapy.

Now, Chris uses her technique to help others with the same condition

and she's working with Louise.

Louise experienced terrible, crippling parosmia.

And so for her, like with many parosmics,

bad smells are just a no-go area and the best way of...

..getting over that is to keep exposing yourself gently

to these things that are causing so much revulsion.

These are what most people would consider bad smells.

Smell training is not a cure for parosmia.

But it has been shown to have one very important effect.

When we lose our sense of smell,

cells in the olfactory nerve are damaged.

I have no idea what that is.

And this causes the olfactory bulb to shrink due to lack of use.

But it appears that by stimulating the olfactory system,

smell training can halt and even reverse this process.

That is the smell of sweaty feet.

Ah! That doesn't smell that bad. OK.

-Would you like to smell it again?

-No, not particularly.

Not now I know what it is.

In order to make smell training useful,

you can't just wave it in front of your nose,

but you have to peer down into each one of these smells and look for

something in it.

Smell training is making a difference for Louise.

Now, more than half the odours she encounters do actually smell the way

they should and she's hoping that gradually more will return.

I don't think I'll ever smell the same way again.

It will always be different but hopefully it'll be better.

Thanks to the remarkable ability of the olfactory nerve to regrow,

Louise is training her brain to smell again.

But the brain is one part of the body that's a long way from being

fully developed when we're born.

It continues to adapt and change into adulthood

as we acquire new abilities.

And I found some fascinating cases that are helping unlock the secrets

of this remarkable process.

This is the hippocampus, an area of the brain associated,

amongst other things, with an ability to navigate.

Now, on brain scans,

taxi drivers are found to have an increased amount of grey matter here,

which is used for processing, and this increases the more time they spend

behind the wheel.

It's proof of the fact that even in adulthood,

learning can change the structure of the brain.

This ability to make cognitive maps is something that in most of us is

developed by about the age of eight.

But in some people,

the ability to build and use these cognitive maps never fully develops.

Anne loves to go walking in the countryside near her

home in Calgary, Canada.

But even a stroll through her local park can be fraught with difficulty.

I get lost all the time.

Even in my own neighbourhood.

Lots of us think we have a poor sense of direction but Anne has a cognitive condition

that means she finds it almost impossible to navigate the world

around her.

She can even get disorientated in her own home.

I don't think people really understand what it's like not to

really have any sense of direction.

It affects my employment, it affects just daily functioning.

Anne's condition has an impact on the entire family.

My mom's sense of direction is nonexistent.

It's absolutely terrible.

When we play sports we always get lost

and everyone knows we'll be late, so no-one wants to carpool with us.

If Anne's going somewhere new,

she always has to have some sort of back-up plan.

She can walk out this door and go two blocks and not find her way back.

It can be that bad.

Anne does use GPS but it doesn't solve the problem entirely.

I like the GPS that's mounted and then I can see sort of visually.

But, you know, sometimes I'm not quite certain which turn to take.

This isn't just a case of someone with a bad sense of direction.

Anne can't recognise the most familiar places

that are part of her everyday life. Even her home is a challenge.

It sounds impossible to believe and until recently

scientists didn't even know that this strange condition existed.

Giuseppe Iaria is associate professor of cognitive neuroscience

at the University of Calgary.

He studies how our brain enables us to navigate.

The most important ability in terms of orientation skills is the ability

of forming mental maps.

The ability to form a map and make use of the map for orientation

requires a variety of complex cognitive skills.

Attention, perception, memory,

decision-making skills, mental imagery.

This ability is fully developed by the age of eight to ten years.

But in 2008,

Professor Iaria was contacted by a woman who described how she consistently

got lost in her own home...

..a place she'd lived in for 20 years.

We knew that people with neurological disorders

or brain damage can actually have problems in terms of orientation.

But having people without any other cognitive or neurological disorder

getting lost every day, that was very new.

Professor Iaria concluded that the woman had simply never developed the

ability to orientate herself,

a disorder that hadn't previously been recognised.

He named it Developmental Topographical Disorientation, or DTD.

To see if he could find anyone else with the same condition,

he went on national radio to talk about the case.

On the radio, when I was listening to this interview,

there was the mention of not having an internal compass

and it's a neurological condition.

I thought, "I've got to get a hold of him!"

We were really surprised by the response we got.

Within one single year we were able to test

and publish a scientific paper,

with 120 individuals affected by this condition.

Professor Iaria has asked Anne to draw a floor plan of her own home.

And then there's the entryway.

Most of us can visualise where the rooms are

and transfer that mental map to paper.

But people with DTD, like Anne, find this task impossible.

So then is this the exit door? Is this the back door?

So these rooms are definitely not all the same size.

No. No, but where it's...

The location is there, yeah.

Yeah.

SHE LAUGHS

To discover why people like Anne are unable to form mental maps,

Professor Iaria has been using an MRI scanner to look deep in their brains.

And he's found something unusual.

To be able to navigate,

we mainly need two parts of the brain to work together -

the hippocampus, where we form maps, and the prefrontal cortex,

where we make plans and decisions.

In patients with DTD,

the professor found these two parts of the brain were not active at the

same time and therefore were not in sync.

We did compare the group of individuals with DTD with a group of

individuals without DTD.

The difference we found was a decreased connectivity

between the hippocampus and the prefrontal cortex.

This is a clue as to why Anne was getting lost all the time.

And there are indications that this runs in the family.

One of Anne's sisters and her aunt also show signs of having the condition

and are now also working with Professor Iaria.

This, and other cases, suggest the cause of the condition may be genetic.

This is a unique opportunity to relate genetics to complex cognitive

functions, not just to medical conditions.

Now, Professor Iaria is working on a treatment, but it isn't a drug,

it's a computer game.

The player learns to navigate between different locations.

The aim is to train the brain to form mental maps.

Those training programmes can actually help also individuals

who have a poor sense of direction,

not necessarily individuals affected by DTD.

Anne now finally understands why she finds it so difficult to navigate

and knows she's not alone.

Finding out that this actually is a condition,

there was a lot of relief and consolation in that.

What's most exciting is that this kind of treatment has the potential

to help patients with dementia,

who lose their ability to form mental maps later in life.

Anne is slowly becoming able to navigate the world

because the brain has the ability to keep changing and developing

through our lives.

But there are some things we're born with that are written into the very

fabric of ourselves and simply won't change without medical intervention.

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,

as happened in our last, remarkable case.

Rhys Evans has made medical history.

The fact that he can live the normal life of a teenager is thanks to a

ground-breaking treatment.

He was a happy baby, putting on weight,

he was really well, but when I stopped breast-feeding him

then he seemed to have little coughs and colds and several chest infections.

These frequent infections baffled doctors.

He was given lots of antibiotics but nothing seemed to do the trick

and I just think he was just deteriorating,

he was losing lots of weight.

As his condition worsened, Rhys was admitted to hospital.

After four weeks of tests, the family received a diagnosis.

Rhys had a rare genetic condition known as Severe Combined

Immunodeficiency, or Scid.

A fault in a single gene meant his immune system didn't work.

As a boy he didn't have a functioning immune system, well,

basically no immune system whatsoever.

So if he went outside or got in contact with other children,

then he could catch anything, which could be fatal for him.

This was a life-threatening condition.

Rhys was transferred to a purpose-built isolation unit at

Great Ormond Street Hospital in London.

He was moved to a very sterile room.

We both stayed in the room with him for what must have been 11 months,

within a very sterile environment.

Being isolated from the outside world protected Rhys from the infections

that most of us shrug off but could have killed him.

To have any chance of a normal life,

he needed a way to repair his broken immune system.

And in the same hospital,

Professor Adrian Thrasher and Professor Bobby Gaspar

were researching a key part of the immune system - white blood cells.

When we're all born, we have to fight infection.

We have to...

be able to live in the world and not get infections

and we need white cells in our blood to do that,

so that's what the white cells do, they fight infection,

they stop us from getting coughs and colds.

And the thing with Scid is that these children are born without

white cells, or white cells that don't work properly.

Magnified a thousand times, you can see the immune system at work.

The large cells are white blood cells.

Here, they are swallowing up some tiny green invaders,

one of the ways they can protect us against infections and toxins.

But Rhys' white blood cells weren't working properly.

Before 1968, these immunodeficiencies were universally fatal.

There was really nothing that could be done.

In 1968 the first-ever child with Scid was treated successfully

by bone marrow transplantation.

White blood cells grow and develop within bone marrow,

so a bone marrow transplant can effectively replace a faulty immune system

with a new one.

But there's a catch.

For a transplant to be safe,

the donor and recipient must have matching tissue types or the

consequences can be fatal.

And for Rhys, no donor could be found.

It appeared that Rhys would have to spend the rest of his life

in sterile conditions, locked away from the outside world.

But there was one option -

a ground-breaking experimental treatment.

Instead of a transplant from another person,

they would take some of Rhys' own cells and alter his genes to correct

the flaw that was causing his disease.

Adrian and I had been working on gene therapy for this particular

condition but we hadn't treated anyone,

we were getting ready to treat a child.

In 2001, Rhys became the first child in the UK to receive the treatment.

First, the doctors took a sample of stem cells from his bone marrow.

Next, they needed to fix the genetic error.

At the time, the only way to do this

was with a specially engineered virus.

It works by latching on to the surface of the stem cell and then

injecting it with new genetic material.

This rewrites the DNA,

replacing the faulty gene with a corrected working copy.

With this step complete,

the modified stem cells were then infused back into Rhys' body.

It was a little tiny bag and he ended up just

having it in a little line in his arm.

Now the hope was that the healthy stem cells would build a whole new

immune system in Rhys' body.

After some weeks at home, he caught a stomach bug.

For his family and his doctors, there was now one burning question.

Would his immune system be able to fight the infection?

The turning point for Rhys was when his own immune system was then

fighting the virus that was in his tummy, and that for us was, yeah,

he is on the road to recovery.

We'd never done this before.

Obviously we'd been able to show what can be done in laboratories

but to actually see it in a child, I mean, it was just fantastic.

We knew then, it works.

This form of treatment actually works, so it's fantastic.

That Christmas, the team at Great Ormond Street received a special video

of their young patient.

Now 16, Rhys lives his life like any other teenager.

I feel like I've won the lottery, really.

I was a lucky number.

I just feel like any other normal person.

For Rhys and a whole generation of children,

Scid no longer means living life in a sterile environment.

You can't give any better gift than life, really,

because you could give anybody as much money in the world as they want,

unless they've got a life to live, there's no point, really.

With modern medicine, we've come so far,

but what these cases have shown me is that our bodies are constantly

growing and developing,

sometimes in ways we're only just beginning to understand.

Next time, we meet an engineer who fixed his own heart,

a girl whose body attacked her brain

and a man who reversed a fatal illness.

That is absolutely phenomenal.

It's a world full of extraordinary people.