A Decade Of The Human Genome

Uploaded by DocumentaryStream on 25.08.2012

Picture a world where cancer is cured with a packet of pills.
Where a single injection treats heart disease,
Alzheimer's, or diabetes.
This is the future that was imagined ten years ago,
when it was announced that a draft of the human genome
had been sequenced.
Scientists had cracked our genetic code,
and had mapped the billions of letters in our DNA.
They hoped that this breakthrough would usher in a new age of medicine.
But Sophie,
and Tom are in search of more than promises.
All three of them have their own remarkable experiences of genetic disease.
My consultant said, "It's literally one in a million.
"You're just extraordinarily unlucky."
And I thought, "Thanks(!)
"That doesn't really make me feel any better."
44 inch waist, 18 stone. Looked like I'd been beaten up,
because the face had swollen up that bad.
In this film, they will go behind the scenes
at some of the world's leading research laboratories
to find out what the sequencing of the human genome has done for them.
They will meet scientists developing treatments
based on the genetic information that was unlocked ten years ago.
Wherever the knowledge takes us, the knowledge will empower us to do more.
Ten years on from the sequencing of the human genome, how close are we
to the life-changing medicines that were dreamt of a decade ago?
Morning, boys. Can you tuck your shirt in for me, please?
Make yourself look nice and smart. COUGHING
Where's your blazer, Lewis? It got set on fire.
Sophie Longton lives a double life.
Do you know what this shape is?
STUDENTS: A trapezium. A trapezium. Excellent. OK.
Mutations in one of her genes means she has to fight to stay healthy.
What about a triangle?
Does any of you know the formula for working out the area of a triangle?
'I love my job, and I really enjoy working with young people.'
A x B x... What have you forgotten? Half. OK.
To see the improvement in a student before and after I've worked with them
is really, really rewarding,
and they really appreciate the work that I do with them.
And I think it's just such a great thing to do.
But only a few people at school know what Sophie endures when she goes home.
From birth, Sophie has been battling with cystic fibrosis -
a disease that affects the lungs and pancreas.
Every day, Sophie has to do hours of physio to help remove mucus
from her lungs, and take dozens of drugs to fight infection.
It is this strict regime that keeps her alive.
One of the hardest things about having cystic fibrosis is just how unpredictable it is,
and just how, even if you do everything possible to try and control your symptoms -
do your physio and take all your tablets and do your nebulisers
and exercise, sort of be like a model CF patient -
an infection can come and take hold, and really you don't have any control over it, in a way.
When I'm feeling run down and when I have a chest infection,
my lungs ache and I produce a huge volume of mucus,
which is a lot darker in colour, so it will be like a dark greeny colour,
and it will look quite thick. And it just seems to keep coming
and keep coming and keep coming, and I cough an awful lot.
Sophie is 23 years old.
The average life expectancy of someone with CF is 38.
She wants to know whether the genetic revolution that occurred
ten years ago might help deliver a long-awaited treatment
before her health declines even further.
At the dawn of the millennium, it seemed that science was on the verge of a new age.
Scientists on both sides of the Atlantic said today
they had completed a rough draft of the entire human genetic code...
Scientists were optimistic, politicians euphoric.
A revolution in medical science whose implications far surpass
even the discovery of antibiotics.
The promises of modern miracles came thick and fast.
It will revolutionise the diagnosis, prevention, and treatment of most,
if not all, human diseases.
Of all the diseases scientists were setting their sights on,
one in particular stood to be transformed
by this new-found knowledge.
An illness that has touched the lives of almost all of us.
WHISTLES Come on then.
Seven years ago, Emma Duncan was diagnosed with cancer -
a disease of the genome itself.
My mother had cancer and died from breast cancer when she was 32.
That was in 1983, and I was nine years old at the time,
and we know that her mother, my grandmother, died from breast cancer
when she was 42, and that was way back in 1966.
Emma didn't know it at the time, but she had inherited from her mother
a rare, mutated copy of the BRCA1 gene.
This significantly increased her chances of getting cancer.
I was in the bath one night, I was 28,
and I felt a lump under my left armpit.
And, for me, I know a lot of women have kind of lumpy bumpy breasts,
but that wasn't me. I'd never had any problems whatsoever,
and I just sat there and had an awful kind of sensation.
It's sort of stomach-churning, and I just thought, "Oh, my God."
'My second cancer was when I was 31.
'It was almost two years on to the day of my first diagnosis.
'It was almost like deja vu.
'My third diagnosis came as a big surprise. I went,'
"How? How on earth can I have cancer again?"
It was three years since my big surgery.
No breast tissue left, had everything removed,
been told I was going to be absolutely fine.
And I just... It was just disbelief more than anything.
My consultant said, "It's literally one in a million. You're just extraordinarily unlucky."
And I thought, "Thanks(!)
"That doesn't really make me feel any better."
Having won her three battles with cancer, Emma wants to find out -
as we all do -
how close we are to fulfilling the promise made ten years ago, that by
understanding our genetic blueprint, we could help defeat the disease.
This blueprint came from sequencing the chemicals that help make our DNA.
Taken together, this is our genome.
It's made of just four chemicals, or letters.
3.2 billion of them.
Mistakes in the order of these letters can lead to illness.
The most common genetic diseases are caused by multiple faults
on dozens, if not hundreds, of genes,
all interacting with the environment.
Tom Fitzsimons is 36.
He lives in Wakefield, West Yorkshire.
A few years ago, Tom started competing in marathons.
It was his way of dealing with a disease
that almost cost him his life.
Easter Sunday was the day we started the race,
and it was like a resurrection for me
To walk towards the start line and have this feeling of,
"Somebody's with me. God's with me,"
and I haven't felt that for years.
In spring of this year, Tom ran the Marathon des Sables,
said by many to be the hardest race on earth.
150 miles in five days, across the Sahara Desert.
'I got over the finish line...
'and a wave of emotion, it just...
'The finish line, you're physically tired,
'emotionally tired. And the first thing I said was,'
"I'm proud to be a human being."
And I hadn't been proud to be a human being for...
It's making me emotional saying it now.
I feel very stupid for saying it, but at that time, it was so...
That's how I felt.
I hadn't been proud of being a human for a long, long time.
I hadn't felt human.
For Tom, completing the race wasn't just a triumph of endurance.
It was a triumph over his addiction to alcohol.
That was really the day when I believed...
I'll never ever say I've beaten it, never ever say I've beaten it.
I always refer to myself as a recovering alcoholic and never a recovered alcoholic,
but it's no longer who I am, I'm not Tom the alcoholic any more.
I'm Tom the marathon runner.
Decoding the human genome offers Tom the prospect of understanding the genetics of his condition.
But it's a huge undertaking.
Just like heart disease, Alzheimer's, and a multitude of other common genetic diseases,
alcoholism is caused by mistakes on many genes,
and their interaction with the environment.
Sophie, Emma, and Tom all want to know whether scientists
have been able to convert their knowledge of the genome
into effective treatments.
How close are we to a cure for cancer?
What hope is there of repairing a single, faulty gene?
And are scientists any closer to understanding complex genetic disorders like alcoholism?
Sophie's come to the Wellcome Collection in London where they have a unique publication.
It's over 100 volumes long,
each with thousands of pages, and text so small it is barely legible.
Together, these books represent one single human genome.
23 pairs of chromosomes containing roughly 28,000 genes.
One of those is the CFTR gene.
We all have it, but in Sophie's case the gene contains some small but significant mutations.
Just four letters are wrong.
I'm just looking at the CFTR gene,
and just thinking that those four letters
have the consequences that they do.
I just can't get my head round it, how such a tiny little thing
in a cell can change my whole life,
and have consequences...
not just for me, but for all my family and all the people around me.
Sophie wants to know how our knowledge of the human genome
is helping scientists develop one of the most exciting techniques in medicine -
gene therapy.
The idea behind gene therapy is a simple one.
First, identify a single mutated gene that is not performing its job properly.
Then insert a healthy gene into the cell to do the job instead.
The CFTR gene was one of the first genes ever to be sequenced
and has been a candidate for gene therapy ever since.
It is a treatment that could, potentially, transform Sophie's life.
She's come to Great Ormond Street Hospital to meet Professor Adrian Thrasher,
one of the pioneers of gene therapy.
The science of gene therapy has seen
really quite dramatic advances over the last ten years or so.
So much so that in the clinic now
there are many trials for different diseases.
So, who has benefited from gene therapy?
Well, this little boy, Rhys Evans, was one of the first patients
we treated at Great Ormond Street Hospital nearly ten years ago now.
Rhys was one of the so-called Bubble Babies,
born without an effective immune system.
Something as simple as the common cold could have killed him.
Unable to find a suitable match for a bone marrow transplant,
he would not have been expected to live much beyond his first birthday
had a novel treatment not been available.
Gene therapy.
Rhys was the first child at this hospital to have gene therapy
because we couldn't find a bone marrow donor,
and this is a picture of Rhys actually on the day of his treatment.
Rhys and his parents have returned to Great Ormond Street for his annual check-up.
It's an opportunity for Sophie to meet someone whose life has been saved by gene therapy.
Pleased to meet you, Marie. Hi, Mark.
Lovely to meet you both.
Where are the terrible boys?
If you can't see them, I'm sure you can hear them.
How old is Rhys now?
Rhys is nine. He'll be ten in September. OK.
Nine years on from the therapy, Rhys has a healthy, strong immune system.
Say hello. Hello. How are you? Fine.
To treat Rhys, Adrian removed a small amount of his bone marrow
and mixed it with healthy copies of the faulty gene.
They then injected it back into Rhys, so the cells
carrying the healthy genes could repopulate his immune system.
They still use this technique today
and have successfully treated over 20 patients.
On the actual day when he received his gene therapy, what was that like?
Oh, it was like Christmas! All the girls in the ward came in and I'll never forget the words...
"This is the golden juice for the golden boy."
Then one of the young girls hooked it up.
And Adrian said, "You make sure he has all of it, mind.
"There's a little bit left in there."
And then after half an hour, it was all over and then it was a waiting game. You wait then.
I remember quite well. It was like six weeks, nine weeks, 12 weeks.
And then you'd have a test every few weeks, and he was getting better
and better, and it was thumbs up all the way in.
He just went from there right up. They said, "He's coming back now."
It's like the old football match. England's coming home, sort of thing. Rhys is coming back!
I mean, I think the important thing that Rhys tells us is that although he was the first,
now, nine years later, we have another tool in our therapeutic medicine box, if you like.
So we know that we have other ways of treating these children -
not just through bone marrow transplantation, but gene therapy.
I'm sure that will become applicable to many other diseases.
But what does this mean for Sophie?
It's incredible what they can do with gene therapy.
Before, I was aware that other conditions such as
the Bubble Boy disease had been treated by gene therapy.
But by actually meeting someone that has been through that experience
and has come through the other side and is now
almost like cured from their condition is fantastic,
but it has always left a big question in my mind.
If gene therapy has been successfully used to treat other genetic disorders
then why isn't it available yet for CF?
One of the boldest claims made when the human genome sequence
was published was that it would help scientists conquer cancer.
Emma's grandmother passed the mutated BRCA1 gene
down to Emma's mother, who in turn passed it on to Emma.
This presented her with a terrible dilemma.
'Deciding to have a family for us was quite tricky.'
It wasn't just an if and when we're going to have a baby,
it was the risk of me passing on a gene fault to that child,
and then the associated risk for when it grew up,
and whether it would develop a cancer or not.
I literally thought I would do absolutely anything to not put
somebody else through what I'd been through, and it's my child, you know.
You would never in a million years wish it on anybody,
even your worst enemy, let alone give it to your child.
When deciding to have a child,
Emma and her husband Graeme put their faith in genetics.
They hoped that one day it would develop treatments capable
of helping their child, Jamie, should he develop a cancer.
So, how close is science to vindicating their decision?
The Sanger Institute in Cambridgeshire.
It's the headquarters of an audacious,
international research project.
Ten years ago, the institute was celebrating its crucial role in helping sequence the human genome.
Today, the DNA sequencing machines have been charged with a new mission
- to sequence human genomes that have developed cancer.
Professor Mike Stratton is one of the world's foremost
cancer specialists, and the man in charge of the International Cancer Genome Consortium.
Their work involves extracting the genome from a cancerous cell
and a normal cell from the same cancer patient.
They then sequence them and compare the two.
And what we're looking for is the difference between the cancer
and the normal.
Because those differences are the mutations, and those mutations
are in those cancer genes, which are driving the cancer.
That's is the information we want to get out.
It took the Human Genome Project almost ten years
to sequence one human genome.
Today, it takes three weeks.
This increase in pace will allow the consortium to examine over 25,000 different cancer cells.
Machines like this, all over the world, is going to take it from a point at which we look upon
cancers as black boxes, to looking inside those black boxes fully lit
to see every detail of how the cancer has developed.
And that is going to change cancer research forever.
Where we're living in ignorance at the moment,
we will have the knowledge, and wherever the knowledge takes us,
the knowledge will empower us to do more.
I think even, for my own selfish reasons as well, for my little boy,
I've been so worried about what the future will hold for him,
so that if he has inherited my gene fault,
we've just got so much more information to be able to deal with it
and to help him make the decisions that he would need to make
in the same way that I had to.
Absolutely. In the spaces of time that we're talking about
with respect to your son Jamie, the 20 years,
we'll be in a completely different position
with respect to our understanding of cancer and the opportunities
for treating and preventing it.
Yeah. That's fab.
So, you got some stuff that you weren't expecting there.
If you can use that? That's good. But that's how it will be.
Oh, God.
It's unbelievable.
Knowledge of the genome allows cancers to be classed not by where
in the body they appear, but by their genetic characteristics.
This means we can put cancers into ever more precisely described sets.
It presents scientists with a huge opportunity
to develop so-called personalised treatments
that target the specific genetics of a particular cancer.
Hey. Don't be silly.
In Wakefield, Tom wants to find out which of his genes contain
the mutations that might help explain why he developed alcoholism,
a disease that took over his life and almost cost him his family.
There was no nights out for me and Zoe,
there was no trips to the cinema with the kids.
It was my cash, any spare cash went on alcohol,
so between 16 and 25 pints a day, more on the weekend,
to the point where I was spending more than I was earning.
The lowest point, I think, was crawling into the kids' bedroom
and taking money out of their money box.
Tom is looking online to see if he can purchase a kit
that will shed some light on his genetic make-up.
"Home Genetic Test Kits UK."
Genetic testing. Diabetes.
Since the genome was sequenced,
businesses have sprung up across the web, offering customers
the chance to identify mutations on just a few hundred different genes.
It's become a multi-million pound industry.
Once his kit has arrived, all Tom needs to do is spit in the vial
and send it off to be analysed.
Tom is hopeful that his test will reveal what contribution his genes
have made to his alcoholism.
Sophie is in London to meet Dr Simon Waddington.
He is using mice to pioneer a radical new technique for delivering gene therapy
that could potentially see cystic fibrosis become a disease of the past.
That's your hat there. Thank you. And then you've got some gloves.
Simon hopes that one day gene therapy will be administered
not to young children, but to foetuses.
So, Sophie, we have three mums here. Come on. There we are.
This is one of the mice here.
So, she's pregnant? She's pregnant, that's right, exactly, yes.
She's about 14 days pregnant, and they give birth at 20 days. OK.
The holy grail of gene therapy is a single injection,
curing the disease permanently.
So, yes, the idea would be a single injection, you could actually target
the gene to the diseased cells, specifically to the diseased cells,
and then hopefully the disease would never occur.
Just one single injection? That's right.
Wow. That would be amazing.
This, of course, is the aim of this. It's very exciting.
At this stage of his research, Simon wants to discover
exactly which cells in the mouse are receiving the new genes.
To learn this, he injects a gene taken from a jellyfish.
It's harmless to the mouse,
but will make the cells that have received it glow fluorescent green.
The greener the mouse,
the more effectively the genes are being delivered.
Come on, you.
I know you don't like it. I'm sorry, poppet.
Sorry, poppet.
So, that blue light highlights the green fluorescent protein?
Yes, that's right. So, if you look down... That's its mouth.
Oh, my gosh! Wow. Really bright. Yeah. Exactly, yeah.
That mouse is expressing the green protein
in nearly all the cells in its body.
So, the gene therapy has been a success?
So, therefore, the gene transfer has been a success in this mouse.
What this means for Sophie is that there may be in the pipeline
a method with the potential for delivering a healthy version of the CFTR gene.
So, if instead of delivering green fluorescent protein,
we delivered, for example, CF gene to express the CFTR protein,
we might, if we do that in a CF mouse,
we might be able to stop the mouse developing cystic fibrosis.
It would be born normal instead.
Very positive.
There you are. That's its foot. Oh, my goodness!
That's incredible. Wow!
'Some people may say that by changing the genetics of a foetus
'whose right is it to do that?
'And some people may say that you're trying to play God.'
But, as Simon pointed out,
that you're only changing the CFTR gene,
you're not changing all the genes in the human body.
You're just changing one tiny one.
And the fact that that will then prevent
such a terrible condition
that will be with that person all their life,
I think it's justifiable.
As a parent, it must be very difficult
to see your child going through CF,
and to think that one... potentially one injection,
one dose of gene therapy whilst my mum was pregnant
could have prevented all of this.
I know that my parents, there's absolutely no doubt
that they would not want me to have had CF,
and have to go through everything I have.
So if it was an option for them,
I definitely think they would have taken it.
Ten years ago,
scientists were surprised by how few genes they discovered in our DNA
But it quickly became clear that fewer did not mean less complicated.
It was the activity level of genes and how they worked together
that scientists had to understand.
Emma wants to see how scientists are changing
the way cancer patients will be treated,
as they extend their knowledge of our genes' activity.
I think having seen how far the cancer genome project has got,
I'm really excited to find out what's going to happen next with that information,
but also what's going to happen sooner rather than later for me.
Here at King's College, London, scientists are working on a method
that, if successful, will change the way they treat their patients.
It will allow them to predict how a patient's cancer will behave,
and with this knowledge, doctors will then know how best to treat it.
Overseeing this research is Professor Ghulam Mufti.
What's been developed at the present moment is, at the time of diagnosis,
you test the cancer cells
and identify what drugs are likely to work or kill those cells.
The hope is to use knowledge of a patient's genetics
to inform the choice of treatment
and ensure they get the best one available.
So for myself, I had a really difficult choice to make
when I had my chemotherapy.
It was either standard treatment or a clinical trial,
but nobody could really advise me that one was going to be
more successful than the other.
With the type of treatment you're offering now,
will that choice become easier for patients like myself?
Oh, definitely. And as time goes on, it's probably going to be the case
that the majority of cancers will have some kind of targeted therapy.
To find the right targeted therapy for the patient,
doctors need to know what's going on in their DNA.
To discover this,
they use a pioneering piece of technology known as a GeneChip.
This reveals the degree to which a gene is active - "turned on" -
or inactive - "turned off" - in a patient's cancer.
Believe it or not, in this little square,
this black box in the middle, it's got all the genes
that a human being has,
so this particular gene chip has over 28,000 genes.
The chip is divided into millions of microscopic squares
and each single square identifies a particular gene.
When molecules from a patient's cancer cell are squirted into it,
the squares are designed to light up
and reveal the level of gene "expression" - or activity -
in the patient's cancer cell.
On the screen is the genetic data taken from a chip.
What is shows you is that there are some of the genes
where the activity is more, and that is represented
by these shining areas, whereas in some areas
there is no activity of the gene at all,
so those are completely dark areas.
The hope is to group cancers by their pattern of genetic activity
and then use this information to take an informed decision
on which treatment will be most effective.
So how long will it be before this technology
is available for patients like me, so that, on an initial diagnosis,
we can be given more information about our treatment choices?
I think that's hard to speculate about,
but one thing is for sure,
that since the completion of the human genome project,
the advances have been absolutely phenomenal and, therefore,
I'm pretty sure that, over a period of time - say, the next decade -
we would be able to identify the right treatment regime
for a particular patient.
The future looks promising.
By studying the patient's genetics,
doctors believe they will be able to produce a targeted treatment
that's most effective for the individual patient.
Finding out that targeted treatment is going to be available is just...
it's amazing, really. My original thoughts
were that there isn't going to be available for 20 years or so.
So to find out that it's going to be within the next decade is brilliant.
Not just for me but also for Jamie as well.
Tom has come to a facility in Oxfordshire
run by the Medical Research Council.
He's here to meet a mouse,
one that should give him a remarkable insight
into his own condition.
What scientists here are trying to do is identify,
one at a time, the genes involved in complex diseases such as alcoholism.
This is Ward 6, where we do most of our work.
We've got about 2,500 cages in here...
They have recently identified one mouse
whose behaviour is unlike anything ever seen before.
So...Tom, this is one of the alco-mice.
This is the one, is it? This is our man.
As you'll know,
what makes us all individuals is the blueprint of life, our DNA,
which is a long genetic code of letters - A, T, G, C and so on -
and that codes every single protein and every single thing in our bodies.
What we've done is we've changed one single letter in that genetic code,
at random, in the animals
and we've looked to see which of them consume alcohol.
We've done that with a simple choice,
very much akin to if you and I went into a pub
and I said, "What would you like to drink?"
So the animals are living very happily in the cage.
And you can see we've got two bottles here - one with water,
and one which is 10% alcohol,
so the equivalent of a strong beer in terms of alcohol strength.
We know that the majority of mice will not touch alcohol at all
if given this choice.
But the alco-mice will take 85% of their daily fluid intake
from the alcohol-containing bottle. Oh, wow.
Which is equivalent to you or I taking, weight for weight,
round about two bottles of whisky a day.
Wow, that's heavy going.
They are, but the important thing is it's entirely free choice,
they can consume whatever they like.
And, as you can see, he's very happy there, having a little look around the cage.
He chooses the ethanol all the time, basically?
85% of the time, yeah.
Scientist have learnt from studies of identical twins,
and of adoption cases,
that around half of what makes people alcoholic is genetic
and around half is their environment.
With the mice, because we are in a controlled environment
where one day is very much like another,
and there are no particular stresses or social pressures or taboos,
these animals are able to make an entirely free choice,
largely driven by their genetics.
So that gene,
that's the one that's saying that this isn't socially-driven,
it's not driven by peer-group pressure,
it is, basically, that's their make-up,
that's the way they were designed,
and that's what they're going to choose? That's right.
From my point of view as an alcoholic,
that's something that is great for me to hear,
that if there is a similar gene in adults, or in humans,
that this gene would say that it's not just my peer-group pressure.
It is the fact that I need to drink and I want to drink.
And it's that I choose, I actually seek drink rather than seeking water.
Scientists have discovered that the alco-mouse gene
is also present in humans.
It's one of the small handful of genes as yet identified,
that are thought to be associated
with an increased risk of alcohol dependency.
It's a small but important step towards an understanding
of the disease that blighted Tom's life for 15 years.
I came in here thinking I was just going to look at a mouse
that had been fed alcohol,
and this one mouse has given me a better understanding, in 15 minutes,
of my own illness
than 15 years of trying to search for answers.
To be told there is a possibility that there is a link
to a signal in my brain that was making me crave the alcohol more...
For me, it's...
I can't get it through how...
both upsetting that it's never been told to me before,
but also liberating that I've got answers
just from that mouse. That one mouse!
Do you want some water? I'm all right, I'm fine.
Just got that off my chest. I'm sound.
Happy. Happy.
That's the thing. Happy.
Identifying genes is one thing.
Using that knowledge to make a medicine that works is another.
It takes around 15 years for any treatment
to make it from an initial idea,
through the trial stages and into the doctor's cabinet.
Gene therapy will be no exception.
I go running because it helps clear all the mucus from my chest.
As I jog along, I'm literally leaving like a trail of mucus behind me,
but if I didn't go running, that would all stay stuck in my lungs.
I just think it is so important that I do everything I possibly can
to keep my lungs in the best possible condition,
so that I will benefit if gene therapy does become a reality,
because I know and I understand that
once a lung damage progresses and gets worse,
it can't be corrected, and the only way I can benefit from gene therapy
is if my lungs are as healthy as possible.
That motivates me to go jogging every day
and to fight as much as I can to keep well.
So that, if gene therapy does one day become a reality,
I will benefit from it.
Sophie's hopes rest with the Cystic Fibrosis Gene Therapy Consortium.
This small, dedicated team of scientists
have been trying to work out how gene therapy might be used
to treat people living with cystic fibrosis today.
The gene therapy consists of man-made copies
of the healthy CFTR gene, suspended in a fatty liquid.
Taking part in the trial is Kevin, who also has cystic fibrosis.
He inhales the gene therapy via a nebuliser.
The aim of the trial is not to cure him, but to work out
the largest safe single dose that could be administered in the future.
Hi, Kevin. How are you? I'm all right. How are you doing?
How does it feel when you're nebulising the gene therapy?
I kind of feel like I'm breathing the future!
This is this crazy kind of chemical concoction
that's been made in a lab that you breathe in,
and it's really incredible what it does.
And it goes in and it changes everything inside your lungs.
Do you feel any different?
Right now? No. I don't expect to feel very different, really, at all.
What motivated you to take part in the trial?
Because it's, um, it's everything
that every science-fiction book I ever read as a kid has promised me.
It's like, it's what was dreamt of in '96 or whenever,
when the human genome project started. It's what was dreamt of.
And it's actually happening!
It's the fruition of all this genetics research.
It's actually giving us a product that can be used. And it's like...
It literally is like Star Trek gene-therapy stuff. It really is!
But there's a long way to go yet.
Lungs are particularly resistant to gene therapy.
They have a massive surface area that needs to be targeted,
and have also evolved to keep out unknown particles.
So thanks to Kevin and his colleagues and friends,
who are going to help us find the biggest safe single dose,
we're now in a position to move forward, probably around next July,
so July 2011,
into this world's biggest trial of repeated application.
We'll then be able to start dosing every month in July
and that will take us, overall, about a year and a half.
So we should be finishing around Christmas Eve 2012
and around that time we'll get a feeling whether this trial,
for the first time in the world,
has shown that patients can actually get better clinically.
That's never been done anywhere in the world.
And thinking of it for myself, is it realistic
for me to think that in my lifetime, I may benefit from gene therapy?
I think absolutely, it is realistic to think about it.
If this Wave 1, this first trial,
looks good at the end of December 2012,
I think we can then move it quite rapidly through into the NHS.
So in terms of timeline, do you know when it may become available?
Can you give a rough idea?
If everything goes fantastically at the end of 2012,
within two, three years, we might be able to put it into regular treatment.
But supposing it doesn't go fantastically,
then it will be much longer.
For me, it almost is like a race against time
and my hope is that gene therapy will become a reality
in the next few years, so I can benefit from it
before my condition gets any worse,
so that it will prevent my lungs from deteriorating any further
and enable me to live a long and happy life.
I know that there will come a point
when there's nothing, really, that anyone can do.
Once my lungs become so damaged, you can't reverse that.
It is quite scary when I think about the future.
I think about how a lot of people with CF end up in a wheelchair,
on oxygen 24 hours a day.
That's a really scary thought
and I just hope I never have to go through that,
because I'll benefit from gene therapy
before my lungs deteriorate that far.
Just knowing that these trials are taking place
and if they have positive results,
and within the next few years we see things progressing,
and in the near future
we can see gene therapy becoming a real possibility,
that's what gives me hope and helps motivate me
to try and keep as well as possible.
After a decade of intensive research,
a new order of medicine is entering the final stage of trials.
That of genetically targeted medicine...
..so-called "personalised medicine".
For cancer patients,
targeted drugs hold the promise of being more effective,
and making the unwelcome side-effects
of traditional chemotherapy a thing of the past.
After the chemotherapy treatment, I just felt really, really queasy,
and that, on top of feeling horrible from the surgery and things,
was just... I just started to feel a bit sorry for myself.
My hair didn't start to fall out until after my second cycle.
In the end, after sort of a couple of weeks, I gave up
and got Graham to shave it all off for me,
which... He found that quite hard, I think.
I just remember being sat in the bath and just crying
and thinking, "This is just, it's just horrible."
I mean, Graham, he did, bless him,
he tried to make me feel a lot better cos he said,
"Actually, you've got quite a nice-shaped head".
And I did!
The Breakthrough Breast Cancer Research Centre in London
is developing a new drug that will treat Emma's type of cancer effectively,
but without inducing the side-effects that she experienced.
It's one of the most cutting edge trials
for the treatment of breast cancer today.
In charge is Professor Alan Ashworth.
Quite barbaric really, the treatment they give you.
It's literally poisoning you from top to toe.
Chemotherapy really just works by killing cells that are growing fast,
and that's why you get the other toxicities.
There's nothing clever about it at all.
Because some normal cells - such as hair, gut, and blood -
grow at the same rapid rate as the cancer cells
the chemotherapy is targeting,
these other cells are also poisoned.
But thanks to his knowledge of the genome, Alan thinks he has found
a weakness in some types of cancer that will be its Achilles heel.
Some tumour cells can't repair their DNA properly.
They actually don't care about repairing it,
they just carry on growing fast,
so what we've worked out a way of doing is trying to exploit that to treat cancer.
Alan's drug inhibits the ability of cells
to repair naturally-occurring defects in their DNA.
At a low concentration, healthy cells are strong enough to survive.
But Alan's breakthrough is that the same concentration
kills cancer cells that are bad at repairing their DNA.
It is an incredibly effective treatment,
and could mean the difference between life and death
for thousands of cancer patients.
So at this concentration here, all the mutant cells are killed,
but actually the normal cells are not really touched,
so potentially that translates into much more powerful treatments,
but much less side-effects as well,
because we're not really killing normal cells.
In fact, in my pocket here,
I have the drug that actually is being trialled now
in people with BRCA mutations, for the treatment of their cancer.
So you can have a look at it, it looks like a fairly bland substance,
but it is very powerful stuff. It's a little white powder.
As you can see on these cells.
Get the right cells and it'll kill them stone dead.
That's just fantastic.
This footage, specially shot in Alan's lab,
shows cancer cells replicating
and then dying as the drug takes effect.
Killing cancer cells while leaving so many healthy cells alive
is a significant breakthrough,
which may mark a turning point in our age-old battle with cancer.
It would not have been possible - at least not so quickly -
without knowledge of the genome.
We're in the 21st century, we've got the human genome sequence,
and we're still treating cancer with medieval treatments.
We cut it out with a big knife, or we burn it with radiation,
or we poison it with chemotherapy.
What we're trying to do is to use the genome information
to develop new ways of treating the cancer itself,
the genetic defects in the cancer, but not the normal cells.
Tom wants to know the results of the spit test he bought on the internet.
He has learnt that one mutated gene can make a mouse alcoholic.
He now wants to know what role his genes played
in contributing to his alcoholism.
Many of the genes Tom was tested for were found through a process
known as Genome Wide Association Studies.
In these studies, genetic data is taken
from people with a particular disease and from people without.
It's then compared and contrasted by teams of genetic statisticians.
They ushered in something of a gene gold-rush,
appearing to identify genes associated with diseases
as diverse as hypertension, obesity and depression.
For some, tests like the one Tom took
represent the progress that genomic science has made
over the past ten years,
and satisfy people's desire to know more about their genes.
Whether or not it will help Tom understand his alcoholism,
he's about to find out
with the help of Oxford University Professor Peter Donnelly,
an expert in genome statistics.
What the test shows is that you're in that middle class.
One of your chromosomes has got an A in the genetic code and one has a G.
And what the research suggests, although it's a bit tentative,
is that someone with your genetic type
has an increased risk - but by about 20%, so it's a fairly small effect -
a 20% increased risk, because of that genetic variant, of developing alcoholism.
So although it's tempting to say, "I've got the gene for alcoholism",
that's not going to be the case.
There won't be a single gene which determines whether people get alcoholism,
there will probably be many, many of them,
each one of which has a tiny effect.
And it's like...if you imagine driving in a car,
which is a slightly risky thing,
if you drive for six miles rather than five,
you're at slightly increased risk, but it's only a slight effect,
and if you stop after five miles,
that doesn't guarantee you won't have the accident.
I feel very deflated, to be quite honest with you,
because it appears they've just picked particular genes
and done small studies on people, and they've done reports,
and from what you're saying, we're not very far down the line
on finding any particular gene that's associated with alcoholism.
It just turns out we couldn't have picked this in advance,
that it's one of the harder nuts to crack, or puzzles to unlock,
in terms of the genetics.
But to use the analogy of a journey or a book,
it's like we're towards the end of chapter one of a great big book.
We don't know what's in the rest of it,
but we've made some progress and we're starting to understand.
Which is great for those in the field, but for people like yourself
who want to know what happens at the end of chapter 18,
we don't know that yet.
I thought it was great when we first did it,
I was really looking forward to the results.
I'm now looking at them and thinking, "I could have done without knowing."
It's good to know that there's a particular gene that I might have,
but it doesn't tell me anything significant to what I knew anyway,
the fact that I was an alcoholic.
It doesn't confirm or deny that at all.
You know, I'm an alcoholic, those genes don't tell me any different.
So it's a strange one.
The problem geneticists face in trying to understand alcoholism
is the same one they face in their bid to understand
other common diseases such as heart disease, diabetes, or dementia.
These illnesses, which many of us will get and many will die from,
are genetically very complex...
..borne of multiple genes subtly interacting with one another and their environment,
in different ways and to different degrees throughout our lives.
Ten years after the euphoria that accompanied the completion
of the human genome project, where do we stand?
Illnesses such as Tom's pose the biggest challenge to scientists.
Sequencing the genome is one thing, understanding it is another.
The complex interaction between multiple genes and their environment
means progress is steady but relatively slow.
However, the problem of finding the genes
and designing genetically-based treatments
is no longer insurmountable.
As for Tom, having run the hardest race on earth,
he is now training to row the Atlantic.
Sophie remains optimistic about the future.
Although new antibiotics are keeping her lungs clearer than before,
a gene therapy that will treat her is still elusive.
The challenge of getting the four healthy DNA letters
into her lungs persists.
Back home with her family, Emma, too, is optimistic.
In the age of the genome, it is our understanding of cancer above all
that is undergoing a transformation.
New ways of prescribing medicine and new treatments
are still a few years away,
but scientists are on track.
Emma has discovered that for her and her son Jamie,
the future is less foreboding.