Horizon (1964–…): Season 47, Episode 5 - Miracle Cure? A Decade of the Human Genome - full transcript
Completed ten years ago, the $4 billion Human Genome Project promised cures for diseases and a new world of personalized medicine. But where are we now? Is personalized medicine and gene therapy just around the corner? Horizon inv...
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.
COUGHING
But Sophie,
Emma,
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?
BELL RINGS
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.
SHE WHEEZES AND COUGHS
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.
RATTLING
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.
Oh!
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.
BOY BURPS
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!
SHE WHEEZES
'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.
Right.
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,
erm...
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.
SHE HAWKS PHLEGM
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.
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.
COUGHING
But Sophie,
Emma,
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?
BELL RINGS
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.
SHE WHEEZES AND COUGHS
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.
RATTLING
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.
Oh!
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.
BOY BURPS
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!
SHE WHEEZES
'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.
Right.
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,
erm...
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.
SHE HAWKS PHLEGM
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.