0:00:02 > 0:00:06We're discovering astonishing things about the human body all the time
0:00:06 > 0:00:08through people who are different from most.
0:00:10 > 0:00:12I'm Gabriel Weston.
0:00:12 > 0:00:15As a surgeon, I've spent years studying the human body.
0:00:17 > 0:00:19And the secrets of how it works
0:00:19 > 0:00:23are often revealed by the most rare and surprising of cases.
0:00:25 > 0:00:29So, I've searched the world to find these extraordinary people
0:00:29 > 0:00:31and bring you their stories.
0:00:32 > 0:00:34This is my heart.
0:00:34 > 0:00:36I'm the only one that has this.
0:00:36 > 0:00:39I'm Jordy Cernik and I can't feel fear.
0:00:39 > 0:00:43My name is Harnaam Kaur and I'm a fabulous bearded lady.
0:00:43 > 0:00:46With the help of the doctors that treat them,
0:00:46 > 0:00:49and some of the world's leading scientists,
0:00:49 > 0:00:54I'll be uncovering exactly what makes their bodies unique.
0:00:55 > 0:00:58I'm going to show you the hidden processes
0:00:58 > 0:01:00that make them exceptional.
0:01:02 > 0:01:03Just look at that.
0:01:05 > 0:01:10I'll discover how they're leading us to the cures of the future.
0:01:10 > 0:01:13When we make a breakthrough like this, it is very exciting.
0:01:14 > 0:01:17And I'll use the latest technology
0:01:17 > 0:01:21to uncover the secrets of their bodies and reveal
0:01:21 > 0:01:26how all of these cases are giving us a new understanding
0:01:26 > 0:01:30of the most amazing natural machine on the planet.
0:01:30 > 0:01:31The human body.
0:01:51 > 0:01:55Despite all the knowledge and technology we have at our disposal,
0:01:55 > 0:01:59medicine is still full of baffling cases.
0:01:59 > 0:02:04Cases that are difficult to diagnose, let alone treat or cure.
0:02:05 > 0:02:07In this programme, we'll discover...
0:02:08 > 0:02:11..why this man can taste words.
0:02:12 > 0:02:15How this woman's body attacked her brain.
0:02:17 > 0:02:20And how this little boy's rare illness was treated
0:02:20 > 0:02:23before he was even born.
0:02:23 > 0:02:26I'm going to discover how these remarkable people
0:02:26 > 0:02:29are challenging scientific thinking, and, sometimes,
0:02:29 > 0:02:33even changing the way we'll treat illness in the future.
0:02:35 > 0:02:38And I'm going to start with the astonishing case
0:02:38 > 0:02:41of a man who invented a new medical procedure
0:02:41 > 0:02:43in order to save his own life.
0:02:49 > 0:02:52Tal Golesworthy is an engineer.
0:02:52 > 0:02:55He has no medical training.
0:02:55 > 0:02:58But when he was told he needed life-changing heart surgery,
0:02:58 > 0:03:01he decided to take matters into his own hands.
0:03:03 > 0:03:05It was fear that drove me, simple as that.
0:03:07 > 0:03:11Tal was born with a condition called Marfan syndrome.
0:03:11 > 0:03:14His body is deficient in a protein called fibrillin
0:03:14 > 0:03:16which helps hold tissues together.
0:03:17 > 0:03:22This had a significant effect on how his body grew.
0:03:22 > 0:03:24I was always taller than everyone else. I could always reach
0:03:24 > 0:03:26the apples higher up the tree than everyone else.
0:03:26 > 0:03:29I could always climb over bigger walls than everyone else.
0:03:31 > 0:03:36But Tal's condition also affected his heart and vital blood vessels.
0:03:36 > 0:03:38In particular, his aorta,
0:03:38 > 0:03:42the artery that carries blood from the heart to the rest of the body.
0:03:44 > 0:03:45Tal's aorta was weak
0:03:45 > 0:03:48and could expand abnormally.
0:03:48 > 0:03:51It meant his artery might rupture at any moment...
0:03:53 > 0:03:55..putting his life at risk.
0:03:56 > 0:04:00Doctors told Tal his only option was major surgery -
0:04:00 > 0:04:04to remove his aorta and the valve that connects it to the heart,
0:04:04 > 0:04:07and replace them with a mechanical device.
0:04:07 > 0:04:10Essentially, they anaesthetise you,
0:04:10 > 0:04:12they open your chest,
0:04:12 > 0:04:13they then...
0:04:13 > 0:04:17literally, cut out your ascending aorta with your aortic valve.
0:04:17 > 0:04:19Stitch in the mechanical valve.
0:04:19 > 0:04:21Close you up. Put you on a ward.
0:04:22 > 0:04:27After the operation, Tal would face a lifetime of blood-thinning drugs
0:04:27 > 0:04:30to reduce the risk of blockage in the mechanical parts.
0:04:32 > 0:04:35I really did not want that, so, at that point, I just said,
0:04:35 > 0:04:38"I've just got to do something about this."
0:04:38 > 0:04:39In his professional life,
0:04:39 > 0:04:43Tal was no stranger to grappling with faulty mechanics.
0:04:43 > 0:04:46So, he decided to approach the problem
0:04:46 > 0:04:49as if it were an engineering project.
0:04:51 > 0:04:55My take on this was, "Well, OK, the pipe's bulging a bit
0:04:55 > 0:04:57"but everything is still working all right.
0:04:57 > 0:05:01"If I can put some sort of support around the outside of the pipe,
0:05:01 > 0:05:04"and stop the pipe getting bigger,
0:05:04 > 0:05:07"I can stabilise the situation and everything will be fine."
0:05:07 > 0:05:13Tal's idea was to make a special sleeve to fit around his aorta,
0:05:13 > 0:05:17to reinforce it and stop it expanding dangerously.
0:05:17 > 0:05:21In this way, he hoped he wouldn't need drastic surgery to replace it
0:05:21 > 0:05:23or a lifetime of medication.
0:05:30 > 0:05:32Tal had come up with a clever concept,
0:05:32 > 0:05:36but he needed to persuade the medical establishment
0:05:36 > 0:05:37that it could work
0:05:37 > 0:05:40and find a surgeon willing to perform the operation.
0:05:44 > 0:05:47Professor Tom Treasure is a cardiac surgeon
0:05:47 > 0:05:49at University College London.
0:05:51 > 0:05:54Tal first met him when he was giving a presentation on surgery
0:05:54 > 0:05:56for Marfan syndrome.
0:05:56 > 0:05:59When he finished, he asked for questions, so I just said,
0:05:59 > 0:06:02"Why aren't we imaging, modelling, CAD modelling,
0:06:02 > 0:06:04"rapid prototyping and making a perfectly fitting implant?"
0:06:04 > 0:06:06And he said, "I don't really understand that,
0:06:06 > 0:06:09"why don't we talk about it?" And that's where it all began.
0:06:09 > 0:06:14I was struck by the completely, sort of, out-of-the-loop idea -
0:06:14 > 0:06:17that it really was a totally different approach.
0:06:19 > 0:06:23Professor Treasure agreed to work with Tal on his proposal.
0:06:23 > 0:06:27Their first challenge was to create a sleeve that would fit.
0:06:28 > 0:06:31You've got to have the shape absolutely perfect,
0:06:31 > 0:06:33and it's different for every patient.
0:06:35 > 0:06:39They made accurate 3D scans of Tal's heart.
0:06:39 > 0:06:43These allowed them to design a lightweight, polyester mesh
0:06:43 > 0:06:45to fit perfectly around his aorta
0:06:45 > 0:06:48and reinforce the weakened artery.
0:06:50 > 0:06:53But there was only one way to find out if it would work.
0:06:55 > 0:06:56I was absolutely terrified
0:06:56 > 0:06:59because I knew what was coming.
0:06:59 > 0:07:01I'd stood in on at least a dozen aortic operations,
0:07:01 > 0:07:03so I knew exactly what was coming.
0:07:03 > 0:07:09In 2004, Tal became the first person to try out his own invention.
0:07:11 > 0:07:14I just think on the day, of course, we were apprehensive,
0:07:14 > 0:07:17but we had spent four years in the planning
0:07:17 > 0:07:20and we knew exactly what we were going to do,
0:07:20 > 0:07:22how it was to be achieved.
0:07:22 > 0:07:25So, this was just putting the pieces together.
0:07:27 > 0:07:31On the 24th of May, the long-awaited operation took place.
0:07:31 > 0:07:37Tal's invention was painstakingly fitted around his own aorta.
0:07:38 > 0:07:42I suppose, one might call it a seminal moment in one's life.
0:07:42 > 0:07:43It was a very...
0:07:46 > 0:07:49It was a very, very big moment.
0:07:51 > 0:07:55But only time would reveal if the operation had been a success.
0:07:55 > 0:07:58Five months later, a scan of Tal's aorta
0:07:58 > 0:08:01showed it working better than ever,
0:08:01 > 0:08:04thanks to his ingenious polyester sleeve.
0:08:05 > 0:08:08Because this was a soft and pliant mesh
0:08:08 > 0:08:11with pores big enough for the body
0:08:11 > 0:08:15to grow in and out of microscopically,
0:08:15 > 0:08:17this mesh became part of the aorta.
0:08:17 > 0:08:20So, the body took it into its own tissues
0:08:20 > 0:08:24and made a good strong aorta where there was a weak one before.
0:08:27 > 0:08:29Now, 13 years later,
0:08:29 > 0:08:33Tal's aorta is still working well and he doesn't need medication.
0:08:35 > 0:08:38And since his ground-breaking operation,
0:08:38 > 0:08:40others have undergone the same treatment.
0:08:41 > 0:08:43The first year, we did one.
0:08:43 > 0:08:45The second year, we did two.
0:08:45 > 0:08:47The third year, we did three or four.
0:08:47 > 0:08:49The fourth year, we did five or six.
0:08:49 > 0:08:53Until here we are, 12 years after the first operation,
0:08:53 > 0:08:54and we've done 22 this year.
0:08:57 > 0:09:02To me, as a surgeon, this is a truly inspiring story
0:09:02 > 0:09:06of a patient who refused to accept the status quo,
0:09:06 > 0:09:09and whose inventive mind and determination
0:09:09 > 0:09:13led to a medical advance that's now saving lives.
0:09:23 > 0:09:26As a surgeon, I can't help but be fascinated
0:09:26 > 0:09:31by a case that's solved by an ingenious new procedure like Tal's.
0:09:31 > 0:09:35But in recent years, a new kind of case altogether
0:09:35 > 0:09:39has emerged to become a driving force in medicine.
0:09:39 > 0:09:42These are some of the most extraordinary
0:09:42 > 0:09:45and mysterious I've uncovered.
0:09:45 > 0:09:49Cases where a person's body, indeed their whole life,
0:09:49 > 0:09:52is shaped by one tiny change
0:09:52 > 0:09:57in a single gene among the 20,000 we all possess.
0:10:01 > 0:10:03Nick Sireau isn't a doctor.
0:10:04 > 0:10:07But he IS on the brink of a medical breakthrough.
0:10:09 > 0:10:12I gave up my job to devote myself to finding a treatment
0:10:12 > 0:10:14for my children's ultra-rare genetic disease.
0:10:18 > 0:10:19Soon after they were married,
0:10:19 > 0:10:23Nick and his wife Sonya had their first child, Julien.
0:10:26 > 0:10:29After he was born, we noticed some red in his nappies.
0:10:29 > 0:10:32We were quite concerned that might be blood.
0:10:32 > 0:10:35So, we got some medical advice.
0:10:36 > 0:10:38So, next day, we went to see our GP
0:10:38 > 0:10:42who got a whole bunch of tests done at Great Ormond Street Hospital
0:10:42 > 0:10:44and it came back with a diagnosis
0:10:44 > 0:10:46of an ultra-rare disease called alkaptonuria.
0:10:48 > 0:10:51Alkaptonuria, also known as AKU,
0:10:51 > 0:10:53is a rare genetic condition
0:10:53 > 0:10:56affecting just four people in a million.
0:10:59 > 0:11:02An abnormality or mutation in a single gene
0:11:02 > 0:11:07causes the build-up in the body of a substance called homogentisic acid.
0:11:08 > 0:11:11It turns bones and cartilage black,
0:11:11 > 0:11:14as we see in this image of an elbow joint.
0:11:15 > 0:11:18With this colour change come harmful effects
0:11:18 > 0:11:23that usually emerge when a person is in their 20s or 30s.
0:11:23 > 0:11:26Over years, it accumulates.
0:11:26 > 0:11:28The cartilage starts to harden
0:11:28 > 0:11:30and becomes four times tougher than plastic.
0:11:30 > 0:11:33So, it's very damaging and the cartilage wears away
0:11:33 > 0:11:36and eventually the bone grinds against the bone,
0:11:36 > 0:11:38so the hips start to collapse,
0:11:38 > 0:11:40the knees start to have problems,
0:11:40 > 0:11:41and the elbows and the shoulders.
0:11:41 > 0:11:44But also, the heart valves start to calcify
0:11:44 > 0:11:46so people start to develop heart problems.
0:11:48 > 0:11:52In 1902, AKU was the very first disease
0:11:52 > 0:11:57to be identified as being passed down in families.
0:11:58 > 0:12:01Yet, over a hundred years since this discovery,
0:12:01 > 0:12:05there was still no effective treatment for it.
0:12:05 > 0:12:07So, when his second son, Daniel,
0:12:07 > 0:12:10was also born with the condition,
0:12:10 > 0:12:13Nick made it his mission to find a treatment
0:12:13 > 0:12:16before his sons reached adulthood.
0:12:16 > 0:12:19We thought we've got about 20 years
0:12:19 > 0:12:22to really develop a treatment, you know?
0:12:25 > 0:12:2720 years to develop
0:12:27 > 0:12:31a new medical treatment from scratch is a tough ask -
0:12:31 > 0:12:34even for the pharmaceutical industry.
0:12:34 > 0:12:37And Nick had no medical background.
0:12:37 > 0:12:41So, how on earth was he going to achieve his goal
0:12:41 > 0:12:45and stop AKU harming his children?
0:12:49 > 0:12:51Nick may have lacked medical knowledge,
0:12:51 > 0:12:54but his job was running charities,
0:12:54 > 0:12:58so one thing he did know was how to raise funds.
0:12:58 > 0:13:02At the beginning there was very little funding available for AKU.
0:13:02 > 0:13:03In fact, there was none.
0:13:03 > 0:13:08Nick joined and became leader of the AKU Society,
0:13:08 > 0:13:10a charitable foundation,
0:13:10 > 0:13:13and threw himself into raising money for research.
0:13:14 > 0:13:18So, I was running half marathons and things, raising funds.
0:13:18 > 0:13:21And in 2005, we paid for the autopsy of a patient
0:13:21 > 0:13:23who'd donated her body to science.
0:13:23 > 0:13:24And this was the first time
0:13:24 > 0:13:27there'd ever been an autopsy of a patient.
0:13:29 > 0:13:34One promising avenue was a drug called nitisinone.
0:13:34 > 0:13:38It was hoped it could stop the formation of homogentisic acid,
0:13:38 > 0:13:42the substance that damages bones and turns them black.
0:13:42 > 0:13:45But early research had been inconclusive,
0:13:45 > 0:13:48much more would be needed.
0:13:50 > 0:13:53The man leading research into the condition in the UK
0:13:53 > 0:13:55is Professor Lakshminarayan Ranganath,
0:13:55 > 0:13:58at the Royal Liverpool Hospital.
0:13:58 > 0:14:01He conducted a trial of nitisinone in mice,
0:14:01 > 0:14:04funded with the help of Nick Sireau.
0:14:05 > 0:14:08By trying nitisinone in the mouse,
0:14:08 > 0:14:11we were able to show that it decreases homogentisic acid
0:14:11 > 0:14:14in a very similar way by more than 95%.
0:14:16 > 0:14:20More importantly, we were able to show that if mice were given
0:14:20 > 0:14:24nitisinone from birth, they never got the pigment.
0:14:24 > 0:14:31And if mice were given nitisinone after a certain age,
0:14:31 > 0:14:33the pigment did not progress.
0:14:35 > 0:14:38The results of the mouse trial were extremely promising.
0:14:38 > 0:14:43But now, a clinical trial in humans was desperately needed.
0:14:43 > 0:14:46We realised we had to do our own clinical trial.
0:14:46 > 0:14:48And what was a very promising drug
0:14:48 > 0:14:50would end up languishing in obscurity
0:14:50 > 0:14:53and patients who'd been very hopeful that they'd have a treatment
0:14:53 > 0:14:55would be just devastated.
0:14:59 > 0:15:02Nick now gave up his job to devote himself full-time
0:15:02 > 0:15:05to raising funds for the research.
0:15:09 > 0:15:15To date, he and the AKU Society have amassed over £20 million.
0:15:15 > 0:15:19They're now conducting a series of clinical trials
0:15:19 > 0:15:24involving patients from across Europe and the Middle East.
0:15:24 > 0:15:28So, the data confirms that the two milligram of nitisinone
0:15:28 > 0:15:33we're using has decreased the homogentisic acid by 95%.
0:15:33 > 0:15:36I'm really pleased to say
0:15:36 > 0:15:38that all indications,
0:15:38 > 0:15:40after three years of using nitisinone
0:15:40 > 0:15:43in the National Treatment Centre,
0:15:43 > 0:15:48is that it's slowing down the disease. So, we're really hopeful.
0:15:48 > 0:15:50These trials are still ongoing,
0:15:50 > 0:15:53but since the initial signs are so promising,
0:15:53 > 0:15:56the NHS has given special permission
0:15:56 > 0:16:00for the drug to be used as a treatment for AKU.
0:16:02 > 0:16:05And the reason that the NHS does this for ultra-rare diseases
0:16:05 > 0:16:08is that it realises that it can be very difficult
0:16:08 > 0:16:11to put together the body of evidence needed
0:16:11 > 0:16:14to get approval for a rare-disease drug.
0:16:16 > 0:16:2013 years after he began, Nick's efforts have led
0:16:20 > 0:16:25to the country's first experimental treatment being available for AKU.
0:16:27 > 0:16:30His eldest son, Julien, is now 16,
0:16:30 > 0:16:34making him eligible for nitisinone treatment.
0:16:34 > 0:16:37We're going to be going to Liverpool in December
0:16:37 > 0:16:40where he will spend four days at the National Treatment Centre.
0:16:40 > 0:16:43Julien will have a whole range of tests - of MRI scans
0:16:43 > 0:16:46and x-rays and everything. And then, he'll be given access to the drug.
0:16:48 > 0:16:51This is a remarkable achievement.
0:16:51 > 0:16:53The drive and ingenuity of Nick Sireau,
0:16:53 > 0:16:56working with Professor Ranganath and his team,
0:16:56 > 0:17:00has pushed medical science to the point where, for the first time,
0:17:00 > 0:17:03there will likely be an effective treatment for AKU.
0:17:06 > 0:17:10I think it's very special that my dad has...
0:17:10 > 0:17:14gone through great lengths to help me and my brother.
0:17:14 > 0:17:17I feel proud and very thankful.
0:17:23 > 0:17:25As Nick's story shows,
0:17:25 > 0:17:29genetic conditions are often extremely difficult to treat.
0:17:29 > 0:17:33But they can offer scientists a rare opportunity.
0:17:33 > 0:17:35Understanding the unusual cases
0:17:35 > 0:17:39where something's gone wrong at the level of our DNA
0:17:39 > 0:17:43can help unravel the secrets of how all of our bodies
0:17:43 > 0:17:44are working normally.
0:17:44 > 0:17:48And that knowledge can be used to discover new treatments
0:17:48 > 0:17:54for all of us, as we'll see in our next intriguing case.
0:18:01 > 0:18:05My name is Pamela Costa and I'm a professor of psychology,
0:18:05 > 0:18:09and clinical psychologist, and I work at Tacoma Community College.
0:18:13 > 0:18:14To take Pam's classes,
0:18:14 > 0:18:18students must be prepared to endure the cold.
0:18:18 > 0:18:22Because she has an extraordinary response to warm temperatures.
0:18:24 > 0:18:25I feel like I'm on fire.
0:18:28 > 0:18:30Pam has a rare genetic disease
0:18:30 > 0:18:33called primary erythromelalgia or EM.
0:18:35 > 0:18:37If she gets even slightly too warm,
0:18:37 > 0:18:39her body reacts in an extreme way.
0:18:43 > 0:18:46The symptoms are pretty much...
0:18:46 > 0:18:51on fire, pain, relentless, unremitting,
0:18:51 > 0:18:53as if your feet, especially,
0:18:53 > 0:18:57your legs, and in my case, my hands and my face,
0:18:57 > 0:19:00are in an incinerator 24 hours a day...
0:19:01 > 0:19:04..that you cannot escape from
0:19:04 > 0:19:07in any way, shape or form.
0:19:08 > 0:19:11Even when Pam experiences temperatures
0:19:11 > 0:19:13that would be mild to most of us...
0:19:15 > 0:19:17..she feels like she's in the middle of fire.
0:19:21 > 0:19:24The pain is always there. And so, it's kind of
0:19:24 > 0:19:28this in-the-background noise, if you will.
0:19:28 > 0:19:34And the daily activity that would exacerbate the pain would be
0:19:34 > 0:19:37if it's above 65 degrees.
0:19:40 > 0:19:41To live with the condition,
0:19:41 > 0:19:45Pam has to be in complete control of her surroundings.
0:19:46 > 0:19:50We put in porcelain, the coolest floor possible.
0:19:50 > 0:19:55Every room, every piece of clothing, is geared towards one goal,
0:19:55 > 0:20:00avoiding heat - even at the coldest times of year.
0:20:00 > 0:20:02These are her winter shoes.
0:20:04 > 0:20:07I get cold, my feet get cold, my body gets cold,
0:20:07 > 0:20:10but I'd rather have the bitter coldness
0:20:10 > 0:20:13than the burning, fiery pain.
0:20:13 > 0:20:16It's kind of choose one or the other.
0:20:19 > 0:20:21Pam's condition is an extreme form
0:20:21 > 0:20:24of what is known as neuropathic pain.
0:20:29 > 0:20:33This is pain that originates at the extremities of the nervous system,
0:20:33 > 0:20:36the hands, arms and feet in particular.
0:20:39 > 0:20:43For years, nobody could explain why Pam's body
0:20:43 > 0:20:45was having such an extreme reaction
0:20:45 > 0:20:48to temperatures that were only mildly warm.
0:20:50 > 0:20:53Then, in 2004, a discovery was made
0:20:53 > 0:20:57that looked like it might not just be able to provide the answer,
0:20:57 > 0:21:00but also potentially be of benefit to the millions
0:21:00 > 0:21:03of other people suffering from chronic pain.
0:21:07 > 0:21:08My name is Stephen Waxman,
0:21:08 > 0:21:11I am a professor of neurology at Yale University
0:21:11 > 0:21:15and the Veterans Administration Hospital in West Haven, Connecticut.
0:21:17 > 0:21:21Professor Waxman and his team made a ground-breaking discovery
0:21:21 > 0:21:22about how we feel pain.
0:21:24 > 0:21:28Electrical impulses travel from wherever pain occurs in our body
0:21:28 > 0:21:31along our nerve fibres to the brain.
0:21:32 > 0:21:36Waxman's research revealed how this process is controlled
0:21:36 > 0:21:39by specialised molecules called sodium channels.
0:21:41 > 0:21:45The way a sodium channel works - it's like a gate that opens.
0:21:46 > 0:21:48So, if you were to touch a nail
0:21:48 > 0:21:53or if somebody were to take a match and put it next to your finger,
0:21:53 > 0:21:57your peripheral pain-signalling neurons
0:21:57 > 0:22:00would sense that noxious stimulus
0:22:00 > 0:22:02and the sodium channels would open
0:22:02 > 0:22:06and that would cause nerve impulses to be generated
0:22:06 > 0:22:09and, in the brain, you would recognise - this hurts,
0:22:09 > 0:22:11it's a painful stimulus, and, hopefully,
0:22:11 > 0:22:15that would trigger a protective response, withdrawal of the limb.
0:22:18 > 0:22:21But Waxman and his team observed that people with EM
0:22:21 > 0:22:25had a genetic mutation that caused a malfunction
0:22:25 > 0:22:28in one particular type of sodium channel.
0:22:29 > 0:22:33What we learned is that the EM mutant channels
0:22:33 > 0:22:37cause pain signalling nerve cells to scream - brrrr! -
0:22:37 > 0:22:41when they should be whispering - bup, bup, bup...
0:22:41 > 0:22:43And so when they should be sending a message saying,
0:22:43 > 0:22:47"I'm slightly warm", they're sending a signal saying, "I've been burnt".
0:22:50 > 0:22:53To understand how the faulty sodium channels
0:22:53 > 0:22:55were amplifying the pain signals,
0:22:55 > 0:22:58Professor Waxman needed to study the DNA
0:22:58 > 0:23:02of as many sufferers of EM as possible.
0:23:02 > 0:23:06His work brought him into contact with Pam Costa and her family
0:23:06 > 0:23:10who were involved with the Erythromelalgia Association.
0:23:12 > 0:23:14They gave him a grant to continue his research
0:23:14 > 0:23:18and also connected him to lots more people with EM.
0:23:18 > 0:23:22With access to more patients and, therefore, more DNA,
0:23:22 > 0:23:24Professor Waxman and others
0:23:24 > 0:23:28eventually discovered more than a dozen different mutations,
0:23:28 > 0:23:30all of which can result in EM.
0:23:32 > 0:23:35Finally, Professor Waxman had identified
0:23:35 > 0:23:37the cause and mechanism of EM.
0:23:38 > 0:23:41A set of genetic mutations,
0:23:41 > 0:23:43any one of which could cause a malfunction
0:23:43 > 0:23:49in one particular type of sodium channel called Nav1.7
0:23:49 > 0:23:52and it cast new light on our understanding
0:23:52 > 0:23:54of how all of us feel pain.
0:23:56 > 0:24:02One thing we know for sure from people with EM is that Nav1.7
0:24:02 > 0:24:06is a key participant in the generation of human pain.
0:24:06 > 0:24:08Not only in people with EM,
0:24:08 > 0:24:13but in people with other neuropathic pain conditions.
0:24:13 > 0:24:17Shingles pain, pain from diabetic neuropathy,
0:24:17 > 0:24:20pain associated with traumatic nerve injury,
0:24:20 > 0:24:22traumatic limb amputation
0:24:22 > 0:24:24where the nerves are actually severed.
0:24:24 > 0:24:29The hope is that having learned that Nav1.7 plays such a crucial role
0:24:29 > 0:24:34in pain, drugs can be developed that inhibit its activity
0:24:34 > 0:24:39that will be useful in relieving pain in all of these conditions.
0:24:39 > 0:24:40And in this respect,
0:24:40 > 0:24:44the first small clinical studies are being done right now
0:24:44 > 0:24:48and the hints that are coming from these studies, and they're hints,
0:24:48 > 0:24:51is that the approach may well provide a new approach
0:24:51 > 0:24:55to treatment of chronic neuropathic pain.
0:24:57 > 0:25:00Waxman's work on erythromelalgia may well herald a new era
0:25:00 > 0:25:04of painkilling drugs for all of us.
0:25:04 > 0:25:05Really nice colonies.
0:25:05 > 0:25:08Cancer and mental illness...
0:25:08 > 0:25:13And Pam Costa now has reason to be optimistic about the future.
0:25:13 > 0:25:18My grand vision and hope for the future
0:25:18 > 0:25:21of erythromelalgia is a cure.
0:25:21 > 0:25:23I'd be happy for a reduce...
0:25:23 > 0:25:27Ideally, in my fantasy, I eradicate the chronic pain
0:25:27 > 0:25:29caused by this disease.
0:25:29 > 0:25:34My hope would be that children would never have to suffer
0:25:34 > 0:25:36from this intractable...
0:25:36 > 0:25:39pain ever, ever again.
0:25:40 > 0:25:44From Pam's rare condition has come a new understanding
0:25:44 > 0:25:47of how all our bodies work.
0:25:53 > 0:25:56For diseases that are caused by faulty genes,
0:25:56 > 0:25:59the Holy Grail is finding a way
0:25:59 > 0:26:04to try and rewrite the genetic code to change the DNA.
0:26:04 > 0:26:07At the frontier of this are stem cells.
0:26:07 > 0:26:11Now, these cells have yet to become a specific tissue.
0:26:11 > 0:26:13They might end up being bone,
0:26:13 > 0:26:16blood or brain tissue, but they're not YET.
0:26:16 > 0:26:20We were all once a ball of embryonic cells
0:26:20 > 0:26:22and from this blank slate,
0:26:22 > 0:26:25all the different tissues of the body develop.
0:26:26 > 0:26:30We know now that stem cells persist right into adulthood
0:26:30 > 0:26:31all over the body.
0:26:31 > 0:26:33They're there in the bone marrow,
0:26:33 > 0:26:37the brain, the heart, the muscle, the gut, the skin.
0:26:37 > 0:26:39In fact, there are lots of these little cells
0:26:39 > 0:26:43all over our bodies that don't yet have an identity.
0:26:43 > 0:26:47They're one of the most amazing discoveries of modern medicine
0:26:47 > 0:26:52and there is one truly extraordinary case that reveals why.
0:26:56 > 0:26:58This is the King family.
0:26:58 > 0:27:01The youngest member is two-year-old Adam.
0:27:01 > 0:27:05He is a boisterous, lively toddler,
0:27:05 > 0:27:07but he was born with a rare condition
0:27:07 > 0:27:09that can make bones so fragile
0:27:09 > 0:27:12that even breathing is dangerous.
0:27:14 > 0:27:16When we brought Adam home from the hospital,
0:27:16 > 0:27:18it was a hugely different experience for us
0:27:18 > 0:27:23in comparison to bringing our other three children home from hospital.
0:27:23 > 0:27:26All of Adam's care needs had to be carefully planned and calculated
0:27:26 > 0:27:29to ensure that we didn't fracture any bones
0:27:29 > 0:27:31while we were doing normal tasks
0:27:31 > 0:27:33like dressing him and changing his nappy.
0:27:33 > 0:27:37That just felt so strange because when you've had the new baby,
0:27:37 > 0:27:40- all you want to do is just hold him. - Hm.
0:27:40 > 0:27:42Oh, sorry...
0:27:44 > 0:27:46SHE EXHALES
0:27:51 > 0:27:53When Fiona was 18 weeks pregnant,
0:27:53 > 0:27:59a routine ultrasound scan revealed something unusual about Adam's legs.
0:28:01 > 0:28:04The radiographer discovered that the femurs were too short,
0:28:04 > 0:28:06they were about three weeks behind on growth.
0:28:08 > 0:28:10It kind of looked like, for all intents and purposes,
0:28:10 > 0:28:11like a little lightning bolt
0:28:11 > 0:28:16which suggested that there were fractures as he was growing.
0:28:20 > 0:28:24Their unborn baby was diagnosed with a rare bone condition
0:28:24 > 0:28:26called osteogenesis imperfecta,
0:28:26 > 0:28:29also known as brittle bone disease.
0:28:30 > 0:28:33The couple were told to expect their baby
0:28:33 > 0:28:35to struggle immediately after being born.
0:28:35 > 0:28:39We had to prepare for Adam not being able to breathe when he was born,
0:28:39 > 0:28:42because, obviously, the brittle bones affect all of the bones,
0:28:42 > 0:28:44including the bones of the ribcage,
0:28:44 > 0:28:47so we didn't know how functional his ribcage would be.
0:28:47 > 0:28:49So, we were, I suppose, the first case,
0:28:49 > 0:28:51the option we were presented with was termination.
0:28:51 > 0:28:52That wasn't an option for us.
0:28:52 > 0:28:56Our next option would be just to continue with the pregnancy
0:28:56 > 0:28:58and have it monitored.
0:29:03 > 0:29:09The prognosis for David and Fiona's unborn baby looked bleak.
0:29:09 > 0:29:12It was clear from the ultrasound scan
0:29:12 > 0:29:15that he had a severe form of the disease
0:29:15 > 0:29:19with his bones already breaking within the womb.
0:29:19 > 0:29:21But then they were given a third option,
0:29:21 > 0:29:23an experimental treatment
0:29:23 > 0:29:26that might just treat his disease
0:29:26 > 0:29:28even before he was born.
0:29:32 > 0:29:37Fiona and David were put in contact with Dr Cecilia Gotherstrom
0:29:37 > 0:29:39at the Karolinska Institute in Sweden.
0:29:39 > 0:29:42She had been investigating a cutting-edge treatment
0:29:42 > 0:29:44for brittle bone disease.
0:29:45 > 0:29:47People with brittle bone disease,
0:29:47 > 0:29:52they have one single difference in a specific gene -
0:29:52 > 0:29:56the codes for a protein that builds the bones.
0:29:56 > 0:29:57And this protein,
0:29:57 > 0:30:02the most common mutation is in a protein called collagen.
0:30:05 > 0:30:09Collagen is the substance that gives our bones strength.
0:30:09 > 0:30:12Without it, they become extremely brittle.
0:30:12 > 0:30:15Highly prone to breaks and fractures.
0:30:15 > 0:30:18It's especially important for a growing foetus,
0:30:18 > 0:30:22as, without collagen, the skeleton won't form properly.
0:30:24 > 0:30:27So, Dr Gotherstrom came up with a bold idea -
0:30:27 > 0:30:32to treat the condition while the foetus was still in the womb.
0:30:35 > 0:30:37What she wanted to do
0:30:37 > 0:30:40was to inject stem cells
0:30:40 > 0:30:42into Fiona's womb,
0:30:42 > 0:30:44and into the unborn baby.
0:30:44 > 0:30:48Stem cells are cells which haven't decided yet
0:30:48 > 0:30:51what tissue they're going to become.
0:30:51 > 0:30:54And so, the idea is if you give stem cells
0:30:54 > 0:30:56in a particular condition,
0:30:56 > 0:31:00those undecided cells will know where they're needed
0:31:00 > 0:31:04and they will develop into the tissue that they NEED to be.
0:31:04 > 0:31:09If we give stem cells before birth,
0:31:09 > 0:31:13we think that they would find their way to all tissues,
0:31:13 > 0:31:17and stay there and help build better tissues and better bones.
0:31:18 > 0:31:21The hope is that the stem cells will control the disease
0:31:21 > 0:31:26by growing into bone cells that can produce healthy collagen.
0:31:28 > 0:31:31Fiona and David travelled to Sweden for the procedure.
0:31:31 > 0:31:36Their baby was sedated inside Fiona's womb.
0:31:36 > 0:31:39And the new stem cells injected into his bloodstream.
0:31:41 > 0:31:45Fiona and David then faced an agonising wait.
0:31:45 > 0:31:48They'd only know how effective the treatment had been
0:31:48 > 0:31:49once Adam was born.
0:31:52 > 0:31:55The birth required a huge amount of psychological
0:31:55 > 0:31:57and emotional preparation.
0:31:57 > 0:32:03- It was like preparing for a hurricane you know is coming.- Mmm.
0:32:03 > 0:32:06We were prepared for the fact that when Adam was born
0:32:06 > 0:32:08that he may not cry at all,
0:32:08 > 0:32:11that he would be brought immediately to be resuscitated.
0:32:11 > 0:32:16So, thankfully, when Adam entered the world, he was crying,
0:32:16 > 0:32:18and it was fantastic to hear.
0:32:20 > 0:32:25Adam's crying was a clear sign that the treatment had been a success.
0:32:27 > 0:32:32So, we were expecting Adam to be approximately a 4 lb baby.
0:32:32 > 0:32:36So, when he was born, he was 5 lbs 11 oz,
0:32:36 > 0:32:39which was astounding. We couldn't believe the chubby cheeks.
0:32:42 > 0:32:44But his brittle bones and fractures in the womb
0:32:44 > 0:32:46had left their mark on Adam -
0:32:46 > 0:32:48particularly in his legs.
0:32:51 > 0:32:53The only way I could describe his legs...
0:32:53 > 0:32:56His legs were so deformed and so swollen,
0:32:56 > 0:32:57they looked like bananas.
0:32:57 > 0:32:59They were curved in like this.
0:33:01 > 0:33:06But since those early days, Adam's progress has been remarkable.
0:33:12 > 0:33:15HE GURGLES
0:33:15 > 0:33:16He can do so many things
0:33:16 > 0:33:19that we never thought he would be able to do.
0:33:22 > 0:33:24With all the activities that he does,
0:33:24 > 0:33:27he's actually been able to straighten his own legs a lot.
0:33:27 > 0:33:29They're still a bit bowed, aren't they?
0:33:29 > 0:33:33But, like, he's so... They're so strong.
0:33:33 > 0:33:36In comparison to other children with severe types of OI,
0:33:36 > 0:33:38he's doing very well.
0:33:39 > 0:33:43I do believe that Adam's remarkable progress
0:33:43 > 0:33:46is due to the transplanted stem cells.
0:33:47 > 0:33:51Next year, Dr Gotherstrom will begin an ambitious clinical trial
0:33:51 > 0:33:53funded by the European Union,
0:33:53 > 0:33:57involving 30 babies with brittle bone disease.
0:33:57 > 0:34:01The hope is that the technique will open up new possibilities
0:34:01 > 0:34:04in treating illness before a baby is born.
0:34:07 > 0:34:08He is really hardy.
0:34:08 > 0:34:11We have four children, and of all four of our children,
0:34:11 > 0:34:13there are varying levels of crazy.
0:34:13 > 0:34:17And he is at the most extreme end of crazy!
0:34:17 > 0:34:19- He loves the craic, basically! - Mmm.
0:34:26 > 0:34:31Stem-cell research is one of the major new frontiers in medicine.
0:34:31 > 0:34:35Unlocking some of the most enduring mysteries of the human body,
0:34:35 > 0:34:40and enabling us to treat diseases that we once thought were incurable.
0:34:41 > 0:34:45And our next case is one of the most remarkable I've come across.
0:34:57 > 0:34:59This is Stephen Storey.
0:35:01 > 0:35:04He's about to take a scuba-diving exam.
0:35:05 > 0:35:08I've scuba-dived all over the world for 20 years,
0:35:08 > 0:35:11and that's been one of my big passions.
0:35:11 > 0:35:14But just a few years ago, this would have been impossible.
0:35:18 > 0:35:21Stephen, in 2013,
0:35:21 > 0:35:24experienced a terrifying moment
0:35:24 > 0:35:29where he went from being a highly active, energetic person
0:35:29 > 0:35:33to somebody who suddenly completely collapsed.
0:35:34 > 0:35:37The word I've used to describe it is I just "melted".
0:35:37 > 0:35:40My strength just dissipated and I slumped onto the floor.
0:35:40 > 0:35:43That was the moment when I realised something was wrong.
0:35:46 > 0:35:51Within three days, Stephen was diagnosed with multiple sclerosis.
0:35:51 > 0:35:54It's a condition in which a person's own immune system
0:35:54 > 0:35:57can attack their brain or spinal cord,
0:35:57 > 0:36:00and it can have many different symptoms.
0:36:02 > 0:36:03Patients with MS never know
0:36:03 > 0:36:07what part of their function will be struck next.
0:36:08 > 0:36:11It can affect both brain and body.
0:36:14 > 0:36:16Within nine months of a diagnosis,
0:36:16 > 0:36:19I was confined permanently to the wheelchair.
0:36:19 > 0:36:22So, I couldn't stand, I couldn't walk.
0:36:22 > 0:36:24I was finding it difficult to get out of bed.
0:36:24 > 0:36:26Difficult to look after myself.
0:36:26 > 0:36:28From being a marathon runner,
0:36:28 > 0:36:33within 18 months, paralysed, in hospital, 24-hour care.
0:36:33 > 0:36:36Which is a pretty dramatic decline.
0:36:38 > 0:36:42Stephen has gone from being confined to a wheelchair
0:36:42 > 0:36:45to being an active man who can scuba dive.
0:36:45 > 0:36:50But multiple sclerosis is a degenerative and incurable disease.
0:36:50 > 0:36:52So, how is this possible?
0:36:54 > 0:36:55This is Basil Sharrack,
0:36:55 > 0:36:57a consultant neurologist
0:36:57 > 0:37:00at the Royal Hallamshire Hospital in Sheffield.
0:37:02 > 0:37:06Knowing that MS is caused by a faulty immune system,
0:37:06 > 0:37:09Professor Sharrack had a bold idea.
0:37:09 > 0:37:12To destroy it completely.
0:37:12 > 0:37:14The best way, probably, to treat this condition
0:37:14 > 0:37:19is to replace the faulty system with a new one which is unaffected.
0:37:20 > 0:37:21His plan was then to replace it
0:37:21 > 0:37:26using a method developed to treat certain forms of cancer,
0:37:26 > 0:37:27which involve stem cells.
0:37:30 > 0:37:34This would be a complex and risky process.
0:37:34 > 0:37:38First, Professor Sharrack's team had to collect or harvest
0:37:38 > 0:37:42healthy stem cells from Stephen's own blood and bone marrow.
0:37:44 > 0:37:47Next, they used a high dose of chemotherapy
0:37:47 > 0:37:50to destroy his existing bone marrow -
0:37:50 > 0:37:54a part of the body where key cells of the immune system are made.
0:37:57 > 0:38:01Finally, they reintroduced the healthy stem cells
0:38:01 > 0:38:03into Stephen's body.
0:38:03 > 0:38:05We give the healthy stem cells,
0:38:05 > 0:38:09which we had already harvested, back into the patient.
0:38:09 > 0:38:11And these stem cells will start a fresh new system,
0:38:11 > 0:38:14which is healthy and unaffected.
0:38:14 > 0:38:18The signs are that if patients are given this treatment,
0:38:18 > 0:38:21the stem cells will build a new, healthy immune system.
0:38:23 > 0:38:25Just over a week after his treatment,
0:38:25 > 0:38:29Stephen began to regain movement he had lost.
0:38:30 > 0:38:33Nine days after the treatment,
0:38:33 > 0:38:37I could consciously choose to wiggle a toe.
0:38:37 > 0:38:40It wasn't a spasm.
0:38:40 > 0:38:41It wasn't a...
0:38:41 > 0:38:44sort of reaction to something.
0:38:44 > 0:38:47I consciously thought to myself to move a toe, and it moved.
0:38:47 > 0:38:51At that moment, I could feel my body was starting to recover.
0:38:51 > 0:38:53At that moment, it made me realise
0:38:53 > 0:38:56that this was going to be an incredible journey.
0:38:59 > 0:39:01As the treatment is still being trialled,
0:39:01 > 0:39:03Stephen is monitored regularly.
0:39:05 > 0:39:09Today, he's meeting Professor Sharrack and Professor Snowden
0:39:09 > 0:39:10for the results of his latest scan.
0:39:10 > 0:39:13- Hello.- Good to see you again, Basil. Hello, John. How are you, sir?
0:39:13 > 0:39:16- How are you?- Come, make yourself comfortable.- Thank you very much.
0:39:16 > 0:39:19So, Stephen, let me just show you the scan.
0:39:19 > 0:39:20So, I'm going to show you, first,
0:39:20 > 0:39:23the scan that you had, initially, before the treatment.
0:39:23 > 0:39:27So, on that scan, the MS lesions, they look white in colour.
0:39:27 > 0:39:29The areas which are white in colour
0:39:29 > 0:39:31are areas of active inflammation,
0:39:31 > 0:39:36and there's a lot of them, really affecting the whole of the brain.
0:39:36 > 0:39:39So, this is the scan from today.
0:39:39 > 0:39:43And we are looking for active lesions, white areas.
0:39:43 > 0:39:45- Wow.- And we see none.
0:39:46 > 0:39:48So, this is very pleasing.
0:39:48 > 0:39:50Wow. I'm blown away.
0:39:50 > 0:39:53That is absolutely phenomenal.
0:39:55 > 0:39:59Stem-cell research is in its infancy,
0:39:59 > 0:40:03in the sense that it's being tried for all sorts of conditions.
0:40:03 > 0:40:07But for MS, it's incredibly exciting.
0:40:07 > 0:40:11Stephen's case strongly suggests that taking stem cells,
0:40:11 > 0:40:14replacing a faulty immune system with a new one,
0:40:14 > 0:40:16can have an incredible effect,
0:40:16 > 0:40:19not just in halting the progress of this disease,
0:40:19 > 0:40:20but actually reversing it.
0:40:24 > 0:40:27Today, Stephen is back in his scuba gear.
0:40:29 > 0:40:33Under the critical observation of an instructor...
0:40:34 > 0:40:38..he hopes to regain his previous diving credentials.
0:40:41 > 0:40:43He's waited over two years for this moment.
0:40:48 > 0:40:50- How do you think you got on, mate?- Wow!
0:40:50 > 0:40:53I can't begin to explain how amazing that was.
0:40:53 > 0:40:55Good news is... Give me a high five. You've just reactivated.
0:40:55 > 0:40:57- Well done, mate.- Really? Wahey! - Well done.
0:40:57 > 0:40:59Absolutely brilliant, fantastic.
0:40:59 > 0:41:00Wow, that means so much, Louise.
0:41:00 > 0:41:03- Well done, you did really well there.- Really? Really?!- Awesome.
0:41:04 > 0:41:06From the condition I was in,
0:41:06 > 0:41:10unable to move, to get myself out of bed,
0:41:10 > 0:41:12to be fed with a spoon,
0:41:12 > 0:41:14taken to the toilet, to now,
0:41:14 > 0:41:16literally two years to this month later,
0:41:16 > 0:41:18being able to scuba dive again...
0:41:19 > 0:41:21It's just joyous.
0:41:24 > 0:41:28Every day's an adventure, and today's been one of the best.
0:41:28 > 0:41:29Um...
0:41:29 > 0:41:32Cycling and swimming and all those things are incredible,
0:41:32 > 0:41:36but this is something I've had a passion for for years in my life.
0:41:36 > 0:41:39And being able to do it again is just...
0:41:39 > 0:41:40transformational.
0:41:53 > 0:41:55To me, this story represents
0:41:55 > 0:41:58one of the great achievements of modern medicine.
0:41:58 > 0:42:00Bringing decades of knowledge
0:42:00 > 0:42:03from the fields of cancer and surgery together
0:42:03 > 0:42:07with the emerging field of stem cells to treat a disease
0:42:07 > 0:42:10long thought to be incurable.
0:42:10 > 0:42:13But for all this new knowledge and expertise,
0:42:13 > 0:42:16there's one vital part of the body whose mysteries
0:42:16 > 0:42:19we've still barely begun to crack.
0:42:23 > 0:42:27Even in this age of cutting-edge modern medicine,
0:42:27 > 0:42:31there's a huge amount we just still don't understand about the brain.
0:42:31 > 0:42:34Thanks to advances in imaging technology,
0:42:34 > 0:42:36anatomists have discovered
0:42:36 > 0:42:39nearly 100 new brain regions in the last year.
0:42:39 > 0:42:43And we know that the brain is made up of 100 billion nerve cells,
0:42:43 > 0:42:48or neurons, arranged like wires in a vast telephone exchange.
0:42:48 > 0:42:51What we're no nearer to understanding
0:42:51 > 0:42:55is how this chemical and electrical system
0:42:55 > 0:43:00produces intelligence, consciousness or creativity.
0:43:00 > 0:43:03And, often, it's when something completely unexpected
0:43:03 > 0:43:07goes wrong with the brain, that we learn something new.
0:43:13 > 0:43:15This is James Wannerton.
0:43:15 > 0:43:19Today, he's sightseeing in the German city of Bonn...
0:43:22 > 0:43:26..something he experiences in a very different way from most of us.
0:43:29 > 0:43:30Glucose and white chocolate.
0:43:32 > 0:43:33Potato wedges.
0:43:37 > 0:43:38Chocolate digestives.
0:43:43 > 0:43:44Madeira cake.
0:43:44 > 0:43:49It may seem like James is obsessed with food.
0:43:49 > 0:43:50Soggy, vinegary chips.
0:43:50 > 0:43:53But, in fact, this is how James perceives
0:43:53 > 0:43:55the street names he's reading.
0:44:00 > 0:44:01I can taste words.
0:44:03 > 0:44:06James has a condition called synaesthesia.
0:44:08 > 0:44:13This is where one of our senses triggers a sensation in another.
0:44:13 > 0:44:16When James sees or hears words,
0:44:16 > 0:44:18he experiences a taste.
0:44:20 > 0:44:22It's like a little eye dropper of food,
0:44:22 > 0:44:23I suppose, would be the best of describing it.
0:44:23 > 0:44:25Dink, dink, dink. Constant drip.
0:44:25 > 0:44:27Ever since I was young,
0:44:27 > 0:44:28I navigated by taste.
0:44:28 > 0:44:31I've learnt the city layout,
0:44:31 > 0:44:32where I live,
0:44:32 > 0:44:34my way to school,
0:44:34 > 0:44:36I learnt it all by a sequence of tastes.
0:44:39 > 0:44:42Every single word has a signature flavour -
0:44:42 > 0:44:44even names -
0:44:44 > 0:44:48and that deeply affects his relationships with other people.
0:44:49 > 0:44:51My friends' names. They all follow the pattern.
0:44:51 > 0:44:54They're all very nice, tasty names.
0:44:54 > 0:44:56I've had plenty of friends called Robert.
0:44:56 > 0:45:01Tastes of strawberry jam sandwiches, for some peculiar reason.
0:45:01 > 0:45:03I would never have a friend called Alan
0:45:03 > 0:45:06because it gives me the taste and texture of dried mucus,
0:45:06 > 0:45:08would you believe.
0:45:10 > 0:45:13There are various forms of synaesthesia.
0:45:13 > 0:45:18All of which involve an unusual interaction between the senses.
0:45:18 > 0:45:22Some people see colours when they read certain letters or words,
0:45:22 > 0:45:24or hear particular sounds.
0:45:24 > 0:45:26But James's version,
0:45:26 > 0:45:28the ability to taste words,
0:45:28 > 0:45:30does seem very bizarre.
0:45:37 > 0:45:40Jamie Ward is professor of cognitive neuroscience
0:45:40 > 0:45:42at the University of Sussex.
0:45:42 > 0:45:45He took MRI scans of James's brain
0:45:45 > 0:45:50to find out what could possibly explain his strange sensations.
0:45:51 > 0:45:55We took words that have particular flavours for him.
0:45:55 > 0:45:57So, we take words that are very intense,
0:45:57 > 0:46:00or words that produce flavours that are horrible,
0:46:00 > 0:46:03or words that produce flavours that are quite weak and neutral.
0:46:05 > 0:46:09When he compared James's brain scans to an ordinary person,
0:46:09 > 0:46:10he saw something remarkable.
0:46:14 > 0:46:15When you or I hear a word,
0:46:15 > 0:46:19a part of the brain called the auditory cortex activates.
0:46:22 > 0:46:25And we understand the meaning of that word using the temporal lobes.
0:46:26 > 0:46:29But that's not all that happens in James's brain.
0:46:29 > 0:46:33Another part that is involved in taste and emotion also activates.
0:46:35 > 0:46:40And a third area lights up that's involved in how we process images.
0:46:40 > 0:46:43So, there's a lot more activity in James's brain.
0:46:45 > 0:46:48This suggests synaesthesia is physical
0:46:48 > 0:46:51and rooted in how the brain is wired.
0:46:53 > 0:46:56So, not only do they have these unusual experiences,
0:46:56 > 0:46:58they actually think differently. They think in images.
0:46:58 > 0:47:01They also seem to have better memory.
0:47:01 > 0:47:03And this might be that they can use their synaesthesia
0:47:03 > 0:47:05to help them to remember.
0:47:05 > 0:47:08But it also seems to be the case that their brain is predisposed
0:47:08 > 0:47:10to form these better connections,
0:47:10 > 0:47:13and hold on to information in a way that other people don't.
0:47:17 > 0:47:20As scientists discover more about synaesthesia,
0:47:20 > 0:47:22they're beginning to use that knowledge
0:47:22 > 0:47:24to help people with sensory impairments.
0:47:26 > 0:47:28People like Daniel.
0:47:28 > 0:47:29He's blind.
0:47:30 > 0:47:33But work being done by Jamie and his team
0:47:33 > 0:47:35is allowing him to build up a picture
0:47:35 > 0:47:38of the world using a different sense altogether.
0:47:40 > 0:47:42So for example, people who don't have vision,
0:47:42 > 0:47:47we might be able to express the visual world to them using sounds.
0:47:47 > 0:47:48As Daniel moves,
0:47:48 > 0:47:52a camera detects the structure and position of nearby objects
0:47:52 > 0:47:54in three dimensions.
0:47:54 > 0:47:58This information is converted into sounds.
0:47:58 > 0:47:59He's going from left to right.
0:47:59 > 0:48:02- Now walking towards me. - HIGH-FREQUENCY TONES
0:48:02 > 0:48:06Changes in volume and pitch correspond to how near or far...
0:48:06 > 0:48:08Going back. Further away.
0:48:08 > 0:48:10..an object is.
0:48:10 > 0:48:11Closer again.
0:48:11 > 0:48:15Different instruments also indicate colour.
0:48:15 > 0:48:19There is a clear distinction between red or green, blue.
0:48:19 > 0:48:21DIFFERENT TONES PLAY
0:48:23 > 0:48:28So, the first sound I can hear on my left is...
0:48:28 > 0:48:29RESONANT TONE
0:48:29 > 0:48:32..a deeper cello sound?
0:48:32 > 0:48:37And I know that this is associated with a blue colour.
0:48:37 > 0:48:40- Then the next one up... - HIGH-PITCHED TINK
0:48:40 > 0:48:45..is a really high-pitched violin sound.
0:48:45 > 0:48:48So, that should be a yellow.
0:48:48 > 0:48:51To some extent, we can think of blind people training themselves
0:48:51 > 0:48:53to be synaesthetes,
0:48:53 > 0:48:57so far as they're taking something that is purely auditory,
0:48:57 > 0:48:59and they're using visual parts of their brain
0:48:59 > 0:49:01to process this auditory stimuli.
0:49:04 > 0:49:08The inspiration for this technology comes from people like James
0:49:08 > 0:49:12and their amazing ability to combine the senses.
0:49:12 > 0:49:14Madeira cake.
0:49:14 > 0:49:16It's a major part of my life.
0:49:16 > 0:49:19It feels very natural and normal to me.
0:49:19 > 0:49:23If I had it taken away, I couldn't remember anything.
0:49:24 > 0:49:27Chocolate digestives.
0:49:33 > 0:49:35Through cases like James's,
0:49:35 > 0:49:39we're learning more about how the different parts of our brain
0:49:39 > 0:49:40connect and interact
0:49:40 > 0:49:44to give us our understanding of the world around us.
0:49:45 > 0:49:50But the brain doesn't always give up its secrets so easily.
0:49:50 > 0:49:52In our final, remarkable story,
0:49:52 > 0:49:55we'll meet a family whose quest for answers
0:49:55 > 0:49:59revealed a new understanding of how our brain works,
0:49:59 > 0:50:03what can go wrong with it, and how we can treat it.
0:50:07 > 0:50:09My name is Emily Gavigan
0:50:09 > 0:50:11and my body attacked my brain.
0:50:16 > 0:50:19I was home for winter break,
0:50:19 > 0:50:22and I had gone to a coffee shop with some of my friends.
0:50:22 > 0:50:24And I was leaving the coffee shop,
0:50:24 > 0:50:27and I was very suddenly manic and paranoid
0:50:27 > 0:50:30that these trucks were following me.
0:50:32 > 0:50:35This paranoid episode wasn't unique.
0:50:36 > 0:50:38In the months before,
0:50:38 > 0:50:40Emily's parents, Bill and Grace,
0:50:40 > 0:50:43had noticed a change in her personality.
0:50:43 > 0:50:48She became really just a different person.
0:50:50 > 0:50:53We actually thought that possibly she was,
0:50:53 > 0:50:56she had gotten into, maybe, drugs.
0:50:58 > 0:51:00We took her to a doctor,
0:51:00 > 0:51:01and they started to treat her
0:51:01 > 0:51:04as though she had a psychiatric illness,
0:51:04 > 0:51:07especially because of the paranoia,
0:51:07 > 0:51:09the aggressive behaviour.
0:51:11 > 0:51:16A psychiatrist prescribed Emily a series of mood-stabilising drugs.
0:51:17 > 0:51:18But nothing seemed to help.
0:51:20 > 0:51:23She was eventually admitted to a psychiatric hospital.
0:51:26 > 0:51:27During that stay in the hospital,
0:51:27 > 0:51:31they were leaning toward the diagnosis of schizophrenia.
0:51:31 > 0:51:35They told us that she would not be able to work again.
0:51:35 > 0:51:38They said that she would not be able to function normally.
0:51:41 > 0:51:43But Emily soon started to show symptoms
0:51:43 > 0:51:46that just didn't fit with schizophrenia.
0:51:48 > 0:51:51My mom and I were headed to the pharmacy to pick up some medication.
0:51:51 > 0:51:56We got out of the car to go into the pharmacy, and I couldn't walk.
0:51:56 > 0:51:59Emily was rushed to hospital.
0:51:59 > 0:52:03Doctors suspected something was causing inflammation in her brain,
0:52:03 > 0:52:05and changed her medication.
0:52:05 > 0:52:08But she had a severe reaction to the new drugs.
0:52:12 > 0:52:14She was in critical condition.
0:52:14 > 0:52:20I asked the neurologist to come back into the room to re-examine Emily,
0:52:20 > 0:52:22to really look at her.
0:52:22 > 0:52:28And Grace asked him if he thought, you know, Emily would die.
0:52:29 > 0:52:32He couldn't say that she might not during the night.
0:52:34 > 0:52:38Desperate for answers, Bill had been reading everything he could find
0:52:38 > 0:52:41that might bring a clue to what was happening to Emily.
0:52:41 > 0:52:42And he'd read a report
0:52:42 > 0:52:46of a young woman with similar symptoms to Emily,
0:52:46 > 0:52:50who was also diagnosed with mental health issues.
0:52:50 > 0:52:55But, in fact, something else completely was going on.
0:52:55 > 0:52:58Her own immune system was attacking her brain.
0:52:59 > 0:53:04So, after they took Emily to the intensive care unit,
0:53:04 > 0:53:08I stayed behind and I asked the neurologist to stay behind,
0:53:08 > 0:53:09and I handed him the article
0:53:09 > 0:53:12that had been written in the New York Post.
0:53:12 > 0:53:14And I insisted that he read the article
0:53:14 > 0:53:18while he was standing in front of me.
0:53:19 > 0:53:21Emily was immediately airlifted
0:53:21 > 0:53:24to the hospital of the University of Pennsylvania.
0:53:26 > 0:53:29This was where the patient Bill had read about had been diagnosed.
0:53:32 > 0:53:36Dr Maria Chen was a neurologist on Emily's team.
0:53:38 > 0:53:40When Emily arrived at Penn Medicine,
0:53:40 > 0:53:43she was in a critically ill state
0:53:43 > 0:53:44as a result of seizures
0:53:44 > 0:53:47and a blood clot that she sustained.
0:53:49 > 0:53:51The doctors immediately suspected
0:53:51 > 0:53:55that Emily had the same condition they'd diagnosed before.
0:53:55 > 0:53:58A rare autoimmune condition
0:53:58 > 0:54:03called NMDA, receptor antibody encephalitis.
0:54:03 > 0:54:06NMDA, receptor antibody encephalitis is a condition
0:54:06 > 0:54:08where your body's immune system
0:54:08 > 0:54:12generates antibodies that inadvertently target
0:54:12 > 0:54:14your body's brain and cause dysfunction.
0:54:14 > 0:54:18NMDA receptors are situated in the part of the brain
0:54:18 > 0:54:21that's important for learning and memory.
0:54:24 > 0:54:27Tests for the condition came back positive.
0:54:27 > 0:54:31Emily and her parents finally had a diagnosis.
0:54:33 > 0:54:36So, Emily was not thinking correctly
0:54:36 > 0:54:41because if this receptor is not engaged and working properly,
0:54:41 > 0:54:43you can have paranoid thoughts.
0:54:43 > 0:54:45You can have inaccurate memories.
0:54:47 > 0:54:49Emily started a new course of treatment
0:54:49 > 0:54:53to suppress her immune system and remove the antibodies
0:54:53 > 0:54:55that were attacking her brain.
0:54:55 > 0:54:57And she began to recover.
0:54:58 > 0:55:01I look like...
0:55:01 > 0:55:03mess.
0:55:03 > 0:55:05- You look like?- A mess.
0:55:05 > 0:55:08No, you don't! I think you look pretty good.
0:55:08 > 0:55:10SHE LAUGHS
0:55:10 > 0:55:15I had to relearn everything from how to brush my teeth,
0:55:15 > 0:55:17how to feed myself,
0:55:17 > 0:55:19how to tie my shoes,
0:55:19 > 0:55:21that kind of basic stuff
0:55:21 > 0:55:24that you don't think about any day.
0:55:27 > 0:55:30Thanks to her father's persistence,
0:55:30 > 0:55:35Emily eventually received the right treatment and made a full recovery.
0:55:35 > 0:55:38But, to me, the end of Emily's story
0:55:38 > 0:55:40is just the beginning of a new chapter
0:55:40 > 0:55:44in our understanding of how the brain and the body
0:55:44 > 0:55:48affect each other, causing symptoms that, even today,
0:55:48 > 0:55:50can be difficult to diagnose.
0:55:52 > 0:55:54Professor Belinda Lennox
0:55:54 > 0:55:58is a psychiatrist at the University of Oxford.
0:55:58 > 0:55:59In mental health, in psychiatry,
0:55:59 > 0:56:03we diagnose people based on the symptoms that they describe to us.
0:56:03 > 0:56:06We have no blood tests. We have no investigations.
0:56:06 > 0:56:08We have no diagnostic tools
0:56:08 > 0:56:10for the serious mental illness
0:56:10 > 0:56:13that I see as part of everyday clinical practice.
0:56:16 > 0:56:19Professor Lennox suspects that some people who are thought to have
0:56:19 > 0:56:21certain severe mental illnesses
0:56:21 > 0:56:24may actually have conditions similar to Emily.
0:56:26 > 0:56:28To find out, she and her team
0:56:28 > 0:56:32screened more than 200 patients across England.
0:56:32 > 0:56:35Almost 10% of them either carried
0:56:35 > 0:56:37the antibody against NMDA,
0:56:37 > 0:56:39or one similar.
0:56:39 > 0:56:41Over the last few years,
0:56:41 > 0:56:44we have been treating people with schizophrenia
0:56:44 > 0:56:46who have been found to have these antibodies,
0:56:46 > 0:56:48with immune therapy,
0:56:48 > 0:56:52alongside their standard psychiatric treatment.
0:56:52 > 0:56:55In our experience, people do get better.
0:56:59 > 0:57:02The results so far are very encouraging.
0:57:03 > 0:57:06And Professor Lennox is about to start a trial
0:57:06 > 0:57:09that will compare the effects of immunotherapy
0:57:09 > 0:57:12against placebo in treating psychosis.
0:57:15 > 0:57:18If successful, it could revolutionise
0:57:18 > 0:57:22the way doctors approach the diagnosis of conditions
0:57:22 > 0:57:24that affect the brain.
0:57:24 > 0:57:28Ensuring that more patients get the right treatment and recover.
0:57:28 > 0:57:29Like Emily.
0:57:32 > 0:57:34Her personality has come back.
0:57:34 > 0:57:38She's that same person who was very outgoing, and very loving,
0:57:38 > 0:57:40and the person that we had before.
0:57:40 > 0:57:43She's just a wonderful person
0:57:43 > 0:57:45and we're very, very happy.
0:57:47 > 0:57:51Going through this illness has definitely changed me.
0:57:51 > 0:57:54It showed me that, sometimes, you do get second chances,
0:57:54 > 0:57:56but not to take them for granted.
0:58:00 > 0:58:03Emily's story is a powerful reminder
0:58:03 > 0:58:07that we're learning new things about the human body all the time.
0:58:09 > 0:58:10And throughout this series,
0:58:10 > 0:58:14we've encountered people who are helping to drive that progress.
0:58:16 > 0:58:19Individuals with superhuman abilities,
0:58:19 > 0:58:24others with incredible resilience when their body goes wrong
0:58:24 > 0:58:27and the doctors who are unlocking their secrets.
0:58:29 > 0:58:34This is truly the frontier of modern medicine, and it's come about
0:58:34 > 0:58:37thanks to some of the most extraordinary people on the planet.