Cancer. It may be years before we solve the problem. Yet, already,
we're quite sure that we'll get there.
In fact, we can say with certainty that one day
cancer will be controlled.
My mum did worry that I spent too much time messing
around with computers and things and not enough time
talking to people.
As a child, the things that I enjoyed most
was taking apart old radios
or bits of electronics and trying to figure out how they worked
and make them do things that they otherwise
wouldn't normally do.
I suppose, the pleasure of a robot builder.
Early suspicion, accurate diagnosis
and effective treatment have brought about marked
reductions in mortality.
Our knowledge of cancer has grown tremendously in recent years.
Do you know I'm making some porridge?
Egg sandwich? Cereal? You want cereal? Go on.
Eventually, I ended up in medical school.
I got really fascinated by haematology.
Come on, let's go.
Come on, come on, come on!
The really nice thing about blood is that you can look at it
under the microscope.
It's very, very tangible.
It suddenly felt very, very familiar.
Actually, these cells were machines.
Like radios that you might take apart.
And, actually, the genetic code is not really that dissimilar
to a computer program.
You're working on one of the most exciting treatments for cancer
in the world right now.
What is the aim of the research you do?
Ultimately, what we want to do is to try and cure all cancers.
A lot of the technology that makes it possible has been developed
but ultimately we depend on the patients entering
our experimental trials.
And there's the man!
It's only when you do the clinical studies that you really know what's
going to work and why something doesn't work.
We're amazingly close.
VOICE RECORDER BEEPS
Graham Threader, hospital number four, one, two, one, six,
three, four, eight.
Graham Threader is a 52-year-old gentleman who has been referred
to immunotherapy clinic for consideration of Car T-Cell Therapy.
Full stop. New paragraph.
He was originally diagnosed in August 2015
following a collapse at home...
..and was found to have leukaemia at that time, full stop.
If you're a patient who's had acute lymphoblastic leukaemia,
the chances are you've been through multiple rounds
of very intense chemotherapy.
You can't possibly work during that time so, you know,
you have to leave your job.
It has huge effects on your family
and on everything else, so it's really very nice for us
in medical science to imagine a time when, actually, you can get rid
of all the really horrible, intensive treatments
and replace them with something that is, you know, for want of a better
word, more natural.
It's a new way of targeting the leukaemia's lymphomas...
You know, and we think it certainly holds
some promise over, you know, the standard
kind of chemotherapies.
This is obviously your... My brother. Your bro. Yeah. OK.
The donor of the moment!
You will get hooked up to the machine.
You know, we collect from you these immune cells.
We genetically engineer them
so they target cancer.
I mean, I guess...
So, my understanding is that you basically...
We take Andy's cells, we weaponise them,
we put them in me and they get to work. Yeah.
So, that is the idea. That is the idea.
So, you have your cells and then we watch you. Right?
And that is it.
And why are we so worried? And why do we want to keep you in?
Well, actually, these cells... I'm sure you've probably looked
on the internet, you've probably seen there are some toxicities.
Right?
There's two things that we worry about in the immediate aftermath
of the cell infusion.
The first thing is something called cytokine release syndrome.
OK?
Basically, you talk about flu.
You know, it's sort of the worst flu you can imagine.
The second thing is there can be irritation of the brain
from this treatment and it's not fully understood.
People don't know exactly why it happens.
A lot of early Car T-Cell development has been done
in the United States.
NEWSREADER: ...on the news that the company is discontinuing
a trial of an experimental cancer treatment known as Car T.
So, there was one study that was run by a biotech company called Juno,
I guess, that was particularly punchy.
This trial was stopped after they saw some deaths
and then restarted after they thought they'd gotten a handle
on what had happened and then stopped again
after they unfortunately saw a few more.
Genetic transformation is what's
causing these deaths? Or...?
Well, first of all, this is kind of a normal part of this process,
which is, you know, trials typically go through real difficulties.
And they have seen some really remarkable
responses in patients.
I've designed my own Car T cells.
You do your best based on what you know from previous studies.
I'm very proud of the fact that we've made Car T-Cell Therapy
available. It's nice to bring this treatment for the first time
to the UK.
I'm quite clear this is the only route that's open to me
to try and survive my leukaemia, so, from my point of view... Yep.
I'm not giving up yet.
Yeah, of course, of course.
And I want to go for it.
One of our issues is that we've got one lab to make these cells.
So in terms of actually making a product for you, we might be looking
at the beginning of November.
We'd be looking then at infusion in December.
Really? OK.
You know, I'm on this recovery medication at the minute. Mm-hm.
I'm conscious that they can't, you know... How can I put it?
You can't keep the plane circling forever.
Yeah, yeah, yeah, yeah.
The trick here is to try to keep me alive until December. Indeed.
Just need to be clear in my head. Yeah.
I've got to go back and talk through with the family...
Yeah, of course. ..where we're at.
Engineering nature is really great fun.
I mean, it's as if somebody is giving you this huge, big
complicated tool kit and you're pulling bits of it out
and putting other bits in and then seeing what happens.
You know, in a way,
biological life on Earth is kind of an alien entity, in a way.
I mean, you could look at it like that. You could look at evolution
as being, sort of, er, an alien intelligence.
All these billions of permutations over time as a sort of
a biological computer crunching away trying to find solutions
to signalling problems.
Problems that cells need to solve.
So, in a way, this computer has been running for hundreds
of millions and billions of years.
And here it is.
And we're just taking what she's done and trying to make
it a little bit better.
Obviously, we grew up together but
this sort of thing you do
for anybody, really, if it's, erm...
..if what you've got is compatible
and that's what they need
I don't think it's much of an ask, really.
I'm very positive and my mind's saying,
"Yes, it's going to be good," although mine's the easy part!
Mine's taken out, so it doesn't really change my body at all.
Like every other...
..cancer patient I've ever met,
you will fight to cling on to being alive.
And you won't let go easily.
So for me,
the risk of doing nothing is that I die.
Simple as.
Do the trial and, you know, it could be brilliant.
Or it could kill me.
The reason it's called a "trial" is because they don't have huge
amounts of data and you only get that from doing a trial.
Someone's got to go first, right?
Otherwise nothing gets done!
At UCL at the moment we're running two trials for leukaemia.
One of them is called the Card study and that's the one that Graham's on.
The trial in total will be between 12 and 14 patients.
The patients are very much in isolation
and not really aware of each other's treatments.
What's Graham's illness done to your relationship?
Has it changed things at all?
Um, I feel very protective.
But you don't need protecting, really, do you?
He's like, invincible - just goes out and does he what wants to do.
I don't think I do that.
Well, sometimes you do. In my... In my mind,
you do things I'd rather you didn't do.
I don't want to be stuffed in an armchair with a blanket over my lap.
I just want you just to take a bit of time out,
so I think you need to have one of those this afternoon.
Yeah, maybe.
Yeah, maybe. See, this is it.
Maybe and then you won't do it,
and then you'll carry on all day, we'll go out this evening
and tomorrow you'll just feel terrible.
People keep saying, what are you doing for Christmas?
I'm thinking I can't think past the end of next Friday
and I'm quite happy that way, to be honest.
But I have bought him - I'll have to show it to you -
I've bought him a special Christmas tree decoration.
It's a guinea pig!
With a Santa hat on it.
Do you see the patients taking part in this trial like guinea pigs?
Yeah, I do, because it's not been done before...
..in this country...
..on patients of Graham's age with Graham's cancer.
Sounds great.
Just wish I could ride it.
First thing I'm going to do when I'm strong enough is take this out.
It's not the same running it in a garage for five minutes.
Keep the battery on charge.
It's a massive step forward but it comes with a complete unknown.
I don't really know how he's feeling.
I think he's just feeling...
No, it's just, because he doesn't want to start going downhill.
He wants to just get in and get in...
Get in the ring and fight it.
And if I'm fit enough to do that, then I'm all right
for Tony's stag weekend.
Yeah.
I mean, he's already talking about going skiing.
Do this with the rugby boys and this with his friends from school,
and in my mind, I'm thinking, you've got to be kidding.
And then in my mind I'm also thinking, yeah - go, you.
Let me demonstrate how Car T-Cell works.
Well, actually, that's a pretty good prop for a cancer cell.
You can use these.
Here we go.
Perfect.
Ping-pong balls.
OK, so this is a T cell and it's one of the main bits
of our immune system that hunts down cells
that are infected with viruses.
That's its main job, is to move around the body looking for any cell
that's infected with a virus.
When it finds a cell that's infected with a virus, it kills it.
These are two normal cells here and this is a cancer cell.
So the T cell's coming around, it's examining these cells.
It's fine so it moves on, and then it examines this cancer cell,
and actually, it's not going to react to it,
because the cancer cell has come from a normal cell.
So as far as this T cell is concerned,
it's just part of our body,
so then it moves on.
So what we do in Car T-Cell therapy, we take a T cell like this
and we take it out of the patient's body in their blood
and then we take it to a special very clean laboratory
where we can make cellular therapies
and what we need to do is we need to reprogram this T cell
to do what we want it to do, and how we reprogram it
is using something called a vector.
And I've got a vector here, a USB key,
so what a vector is essentially is a modified virus,
and what we use the vector to do is to plug in a new piece of DNA
into the T cell, and a new piece of DNA
contains a new computer program
and tells this T cell to behave differently.
In this case, to make a new protein on its surface
and then it becomes - hey, presto - a Car T-Cell.
We inject this back into the patient
and again it does what it normally does.
Going around looking at cells, and this time when it comes
to the cancer cell, it doesn't ignore it any more,
because we've reprogrammed it, so now it's going to recognise
this cancer cell and it's actually going to kill it.
And then what this T cell does is, after it's killed the cancer cell,
it can actually make copies of itself and then it moves around
and keeps on going looking for other tumour cells.
So that's Car T-Cell therapy in a nutshell.
Mahmoud, he's on a different trial to Graham.
He's the first patient on this study
and he's the youngest patient we would recruit.
OK, so that's going to be your line that goes out.
You might feel a little bit dizzy.
The blood pressure can sometimes change
just because we're taking blood out of your system, you know,
and replacing it.
On this trial, we actually use his cells to manufacture
the Car T, so we're not involving a donor.
What do you know about what's happening to you today?
Well, the machine is taking my blood.
The white blood cells, they're collecting it
so that they can modify them.
Change the white blood cells so that they can put them back
into me and then hopefully they will attack my leukaemia cells
if they're detected.
And that will cure my cancer.
I first met Mahmoud when he was having salvage treatment for relapse
of his leukaemia.
He then went on and had a bone marrow transplant.
Unfortunately, he then went on to relapse post the transplant.
His outlook - without treatment, he would deteriorate within weeks.
This is the best way to get him a shot of having a long-term cure.
Can I have work sent from maths, physics
and BTEC business?
Maybe when I come back to school, you could organise a party.
Return party.
OK, thank you, bye.
I've always hated going to secondary school but I miss school now.
Miss it a lot.
And what are you doing with your time
at the moment if you're not at school?
On my laptop playing games
or my Xbox playing games or watching YouTube.
I'm not allowed outside because of my immune system.
I'm not usually this weak.
Very athletic, energetic person.
Not in the morning, but throughout the day.
If this treatment works - and I'm begging it will -
go back to normal life.
Just live, I guess.
Just want to live.
I guess there are bad thoughts that it won't work.
Be heartbreaking for my mum, cos...
..I feel like it's my last hope.
My doctor, Dr Carpenter, has been very supportive.
Do you trust them? Yep.
Who else can I trust?
There are time lags in manufacturing these products.
One of the biggest worries with Graham is keeping him alive
whilst we wait for the lab to manufacture his brother's cells.
We're using a drug called Dasatinib.
But his disease is very aggressive.
At the moment it seems to be working,
but I'd need to see what's happening in his bone marrow.
What's happening, you know, effectively at the site of disease.
A bone marrow investigation gives us the most accurate read
of degree of disease down to a molecular level.
OK, so just going to pop some anaesthetic under the skin.
Is that sharp?
Ah! Sorry.
All right. This bit is going to be painful, OK?
OK?
The leukaemia cells are advancing and overwhelming
all the normal blood cells.
It's a biological battle, it's ongoing.
I'm just going to check the sample, OK? You've done really, really well.
How was that?
Huh!
Don't take this the wrong way, but I don't recommend.
It's just the whole thing's just not a fun day out. No.
Hey, guys!
MUSIC: September by Earth, Wind and Fire
This is what I have to put up with.
Where are you going tomorrow? Margate.
We're going to have a little holiday. For a day.
Look down there at the sign.
"First aid."
Yeah, that might be your saving grace.
Shall we go right, then?
Found a shell. If I put this to my ear, I can hear the sea in it.
And if I take it away again, I can still hear the sea.
How does that work, then?
You're just not funny any more.
LAUGHTER
Why is your back bad?
Don't know.
Mum, any guesses?
Tiles.
Tiles that went upstairs in a big box carried by
somebody who shouldn't have been carrying them.
Unfortunately, the Dasatinib stopped working.
The leukaemia cells have outsmarted the drug.
They've come back and they've completely occupied
the entire marrow.
You get a lot of this stabbing pain in all your bones,
and your big bones and your shoulders
and your hips and your spine and your ribs
and your legs.
Anywhere that produces bone marrow was really kicking off big time.
He actually thought he was going to die in the night.
And the bit that was bugging him about that was he wasn't prepared
to die until he'd given it a go,
until he'd done the trial and then at least he could go out
knowing that he did it.
The fact is your brother's cells behaved really well in the lab.
They've got three doses to be able to give you.
It's here in the hospital
and as soon as we're given the nod we can get started with that.
We've got to pull out everything that we have available to us.
We'll have to use steroids,
we'll have to use chemotherapy...
..in as much as he can tolerate,
to try to suppress things, control things,
to get him to the start line.
It's weird.
Your body, it just tells you stuff.
I had this mad thing in my head a week before.
For some reason, I just had to get these letters done
for Mellie and the kids. Don't ask me why, I just had this thing.
I just need to do that and I'd done it a while ago
but I needed to do it again.
I can't describe to you what drove me to do it,
but something inside me knew that it was all going tits.
I'm very lucky.
My kids can open these letters and know how much I really love them.
It's in the file called "just in case".
Hopefully they won't be reading that for a long time.
This is why this thing is so important.
If this treatment works, it can sidestep some other shit
that at the minute we will have to go through.
Because that will be redundant.
Big prize for this if it works.
Turn on your side.
Mahmoud's taken a fair beating.
The chemo and all the infections,
you know, it takes its toll.
He came in today for another blood test despite the fever.
That has had the effect of delaying having his Car T cells.
It'll just be a case of trying to find that sweet spot
to just give the cells before things do start to unravel.
Mahmoud, if I leave him,
he's very, very nervous.
With a trial, I feel...
..this is the only hope he has.
I think so.
It's something new and you want them to do some magic.
You have a list of questions or things you want to go through?
Once he's had the Car T cells,
when will we know that something is happening?
Yeah. He's getting better or it's working or it's...
If you do get fevers and other reactions that we think
could be the Car T cells at work, then that might be an early sign
that we can see that things are actually happening.
Like this cytokine release syndrome,
which you may have heard that term already,
but that is one of the things that we are wary of
because this is a treatment after quite a lot of treatment.
Then, you know, it is something that can be a risk.
A risk, yes. That's fine.
It's not a risk. You're saving him.
You're saving him.
It's not a risk for Mahmoud.
There are definitely risks involved
but we know the risks of not doing this are much higher.
I mean, that's the weird thing about all this.
One minute you're completely and utterly smashed
and then they come in and say, "Do you want to go home?"
And I'm of course going to say, "Absolutely, yes."
I've probably had these from when you were a little kid.
Christmas is three sleeps away.
I like Christmas a lot. Do a bit of cooking.
I've got my Brussels sprouts recipe, that's nailed down.
Drive them mad with my favourite films -
I always watch The Polar Express.
Probably watching a bit of Chitty Chitty Bang Bang, as well.
I'll probably be doing all of that on my own,
although be nice to have a bit of company.
But kids are a bit, "Oh, is he watching that again?
"Every year he watches it."
But it's Christmas.
So this is the...
This is the guinea pig.
Which I just thought was the funniest thing ever.
I don't think he found it quite so funny.
What's the likelihood of finding a guinea pig with a Santa hat on it?
Honestly.
Where's the guinea pig?
Hands up who got the most presents.
I probably did, actually.
I've had a very lovely day, today.
Happy Christmas.
You would never put yourself through this whole process
if you didn't believe in this.
Huge teams of people involved in every step of the way.
Getting agreement to host the trial,
to develop the science behind it all.
Teaching medical and nursing staff to deliver these therapies.
Teaching the intensive care people what they need to do.
And all of the hoops that Graham's had to jump through,
we all sat here with our fingers crossed.
Phase one studies, we are learning as we go.
And, you know, you can't know it all before you start.
I guess that's the purpose of the study.
We'll have to do this every day. Sure.
The purpose of the test, obviously, as you know, one of the side effects
of the Car T cells is it can have neurological toxicity.
This is what we will then use to compare
to see if it gets any worse after we give the cells.
Can you count backwards from 100 in sevens?
93. 86.
79.
72.
Can you say as many words as possible as you can think of
that begin with the letter F.
Fox, fridge, fix,
fidget, feather, fan, flower...
Is there anything from your perspective,
any other worries you have or concerns? No, it's fine.
Looks good.
Hello! Welcome at last.
I'm Claire. I'm one of the doctors, pleased to meet you.
All right, so they'll basically just hang the bag.
They want to get every last cell out
and once they've infused, it's a case they'll start watching you
by the clock and taking your temperature and blood pressure
and all that stuff.
Total volume is 10.32, bag one of one.
OK.
Right, they're in.
Bombs away.
Graham has got disease on board.
You can actually see the leukaemia cells just by looking at his blood.
It's mixed feelings.
Yes, there's lots of target,
yes, his Car T cells will get the signals perhaps that they require
to expand to have an anti-tumour effect.
But we are very aware and vigilant for the toxic effect of the cells
because the more disease there is,
the more likely there will be toxicity.
Smile.
You can't be in this game if you're not an optimist.
We've done testing in the lab,
we see that it kills CD19-positive targets.
To be fair, in a dish in an incubator.
But, you know, this gives us sort of faith
in the biology, at least.
So he's got about 50% leukaemia cells,
but he has made his way onto intravenous antibiotics
because of the intermittent fevers.
We are hydrating him, aren't we?
He's brilliant, actually.
He's religiously going for the four litres of fluid a day.
He's probably keeping it by his bed
because he's in there like, you know, recording every drop.
Of his urine output?
Of everything.
Claire tells me you've been brilliant at drinking
and keeping your fluid intake up.
We did eight litres yesterday. OK.
In and out. OK.
That's extraordinary.
So, look, day three.
How are you feeling?
Kicking off. OK.
The pain's started to come through, it's like a throbbing pain,
so every time my heart beats, you can feel it.
It's like a stabbing pain.
It's like when I relapsed.
And again.
All right.
We know that the Car T cells tend to expand in your blood
and they expand more vigorously
the more leukaemia cells there are around in the body
to act as a target for them.
In you, what we hope is happening is that those Car T cells
from your brother are actually...
They've circulated, they've passed into the bone marrow.
They've found the leukaemia cells and they're starting to attack them.
That will result in quite a lot of pain.
There is a small possibility the Car T cells have been infused
into you and they aren't managing to expand
or kill the leukaemia cells.
We always have to accept that's a risk,
particularly when we're trying these new medicines for the first time.
Now, the time when we see the maximal number of Car T cells
in your blood is about seven days after infusion.
So the really hard thing for the next few days
is when you're feeling anxious and scared that the leukaemia
might be marching on.
Actually, we just have to hold tight.
We probably won't know until at least a week
and maybe a little bit longer.
He's got bone pain, which we can potentially manage.
Yes. He's not going to get leukostasis, you know.
Well settled. We don't know yet.
If it's just the leukaemia on its own then I'll be a bit pissed off.
If it's the new treatment,
then I'm quite happy to take the pain
because at least it's getting me somewhere.
How do you see the next few days panning out?
Rough.
Now it's starting. Now the fight's starting.
Just repeat the sentence after me.
The cat always hid under the couch when dogs were in the room.
The cat only hid under the couch
when dogs were in the room.
400 million Car T cells.
Seems like quite a lot, doesn't it?
Faith, family, friend, future, fortune,
forgive and forget.
Finally, forbid.
OK, that's enough.
The cells are in, circulating around somewhere.
If there's anything you're worried about,
any new symptoms, we want to know.
Any problems with headaches, you tell us.
Any issues with your vision, you tell us.
Tell me what Mahmoud was like as a boy.
He was very... No. No, no, no.
Very quiet and shy.
And didn't have friends until year seven.
No. No.
OK, I'll be quiet.
Has it always been the two of you growing up?
It has always been the two of us.
I had my daughter because I was worried he was going to be a loner.
What about Mahmoud's father?
He left him when he was...
..three months.
She's my everything.
I guess.
Someone that understands what I'm going through,
so I cherish every time I'm with her, even though I don't show it,
and I can be annoying and everything,
but it's just my way of saying...
..I need you.
He's had a rough weekend.
Over the course of the last 24 hours,
he has developed a sort of further increase in his fever
to about 40 degrees,
and he's getting increasingly short of breath.
He's really, really struggling.
I think it's got to quite a dangerous level now.
He's always going to give it one last extra push
and then another one after that, so it's never his last push.
He's got a plan.
You've just got to go with the plan
and that plan is to do this.
OK. Starting from 100,
can you subtract seven?
Yeah, 93.
86.
79.
73.
72.
I've designed these treatments
almost like you might design a computer program
or an electronic circuit - you kind of pick different components.
At some stage in the design process, you have to say,
"Right, this looks good enough.
"Now we're kind of going to go with it."
If you can tell me words starting with the F letter.
Flip flop.
Four.
Ford.
The issue of course to consider here is brain function.
I mean, you can see the beginnings of neurotoxicity.
We have to have a low threshold to sort of start
that thought process going on
if he remains in this state.
Often you're kind of wondering,
when these treatments are inside the patient and doing their thing,
is, gosh, what if I'd used something slightly different here?
Or what if I'd done this the other way round
or used a slightly different component?
Would that have been better for the patient?
So it is quite a responsibility to have these little
computer programs running inside these patients.
How long has he been shaking for?
Overnight.
Overnight. They've given him Pethidine
and the temperatures have been up and down.
He hasn't slept for even 30 minutes the whole night,
it changes too much.
You have to pray, that's all I can say.
It's through prayer and then the medicine and the doctors
that Mahmoud gets better.
That's what I believe.
Is that more your faith in God or your faith in science?
I think I'm combining both.
I'm sorry you're not feeling well.
You all right? Yes, I am.
So what's going on at the moment,
it's possible that this could be down to the Car T.
We will look today in the lab
and see if we can see the Car T cells in your blood.
We gave that boy 400 million Car T cells.
We give him 400 million Car T cells on Monday.
Yeah. Right. That's not, like, an insubstantial dose.
I'm champing at the bit here.
You're really making me wait here. Come on.
So the Car T cells are there.
And they're there with force.
You actually, of all of the immune cells that are in your blood
at the current time,
70% of all of those are Car T cells.
It's quite something. 70%.
And that is probably why you're feeling hot.
There is something going on.
How long will it take
to get the results back from the lab, do you think?
For the trial.
Claire will take the labs. OK.
We need them today.
All the markers in the blood that we associate with Car T cells
have gone up. Oh, right. Is that good?
No, no. The markers, the inflammatory markers,
but when we actually look for the Car,
we still haven't seen it today.
But it doesn't mean that it's not there, Graham.
I mean that's... Because everything about you at the moment
is suggesting that it is.
He's been quite fearful of falling asleep in case he passes out.
Because you look so poorly now,
I don't think it's fair to make you carry on in this way.
I'd prefer to just try and take the edge off this fever
and if we take the edge off the inflammation,
we might see an effect on your chest as well.
He's suffering.
I think we'll be duty bound to do something to try and...
..control that in some way.
Which would be this drug, Tocilizumab.
It's administered just via a drip.
It's impossible to be 100% sure that Tocilizumab will not interfere
with the potential anti-tumour effect of this Car.
But I also want my patient to be alive
and not on intensive care
and, you know, these are the sort of other considerations.
He's shivering.
How are you feeling?
Cold.
Yeah. Was it a lot?
It's too much.
LIFT: Going down.
Sorry, don't worry. You're just being transferred.
Be good to get you some sleep, wouldn't it, at some point today.
I think at the moment we'll just make sure that we don't need
to intervene to try and dampen down the Car T cells,
but we just need to keep reviewing
to make sure that things stay stable.
There are lines in the sand.
We wouldn't want to see him starting to develop the requirement
to have additional oxygen.
That's all building a picture that the Car T cells are really behaving
in an aggressive way and causing him problems
that we need to turn back.
I think it's good to give it time to work.
I've come a long way for this
and he has come a long way for this.
If they switch it off and it's not done its job,
that's a worry.
He's had his rescue drug to save his symptoms getting worse.
But he still is suffering terribly with his chest.
Feels absolutely dreadful.
You know, last night I was having some quite dark thoughts.
I'd hate to think that he was just being used as an experiment.
Just to scrub the whole thing is a bit of a...
..horror story, really.
But I couldn't stay at the hospital any longer.
I needed to come home.
He's getting very...
..stressed, so I thought actually he'd probably be better
being like that on his own for a bit, and I think, really,
the hope is that the chest will settle down.
But I actually don't think that some of the trial team have
the answers either, because it's a trial.
So part of me is thinking, why on Earth did we do this?
And part of me is thinking we've just got to keep going.
None of it is in his control.
It's entrusting your entire life and future
into the hands of this team,
without knowing what the outcome could be.
A day, a month, a year.
And as Graham always says, you know, I'm doing it for the family,
but, you know, he's got to do something for himself as well.
And if it were just for the family, I would say...
The suffering bit is just awful.
It's really awful watching somebody go through that.
Well, I have to say you look very comfortable now.
We haven't actually had to give you any drugs
to try to control this cytokine release syndrome.
Actually, you've done really well on your own.
Mahmoud's experience to date has been very different to Graham's.
It's easier to treat younger adults
because, unlike the older population,
their bodies are more robust and they can tolerate
the very intensive therapies that we have to throw at them.
So who are these two, then?
My sisters.
Lena and Nian.
Who's the older one? Lena.
It's her birthday on Tuesday.
8, 9, 10.
Got her a present?
I'll get her a present when I'm out of here.
I don't know what to get her.
What do you get a five-year-old?
Do you miss them while you're away?
They're annoying but, yeah, I do.
He's cut his hair off.
He's cut his hair off. Yeah.
Do you like him like that?
Yes.
I suppose our next hurdle to consider is,
what kind of disease impact has this dose of cells had?
We're about day 14 today,
so we've got another 14 days until we can actually evaluate
his bone marrow and see what kind of impact
it's had on his leukaemia.
Do you want to say bye to Mahmoud?
Bye, Mahmoud.
See you later.
High five.
Hello.
How's your week been? I've had a good rest, but it's nice to be back.
I know that sounds weird!
It's quite weird. Yeah, yeah.
You don't look - compared to yesterday afternoon -
like your breathing is more easy.
I had a better night last night.
Did you? Yeah.
OK.
So I think clinically at the moment,
the leukaemia cells never went away totally.
I think we can't say for certain
that another dose of the Car T cells
will work in a significantly better way than the first dose.
And the other thing,
the big elephant in the room,
is that...
..your chest at the moment is slowly getting worse.
That would have to go away completely, wouldn't it,
to be able to... Well, I think infusing a load of T cells into you
with very severe respiratory problems,
I think you wouldn't survive them.
Kill me. Yeah.
I think we're up against it.
And if it worsens still?
I think if your chest worsens,
I think it's grim.
OK.
I'm trying to be honest.
For example, I think if you ended up ventilated on a breathing machine,
I don't think you'd survive.
I don't want that.
And typically...
..how long between...
..chest failure and heart failure?
I don't think it would be very long.
Hours, days?
I think probably hours or days rather than days or weeks.
I mean, you've been watching everything
that's been happening and...
Have you got any questions?
Are you sure?
Do everything we can to try and sort my lungs out.
Overnight last night, his chest got worse,
so he went from two litres of oxygen to needing 35.
So he's on a mask with 35%.
His chest sounds worse.
It's just very noisy and crackly.
From a trial perspective,
he's received the therapy
and he had a transient response.
You know, that's the best that we can kind of say
at the current time on day 17.
We didn't ever guarantee that we would see responses.
We were sort of hopeful that we would see a response,
but it's such early work
and this study is designed to see whether there is toxicity associated
with giving these cells.
Do you feel any sense of responsibility?
Yeah. I mean, I guess the reality is
that, you know, I can't help my personality
and I particularly, you know, I'm very sort of, like, passionate
about this. I do feel that this therapy, you know,
is really important to the future of haematology and...
And I probably, to some extent, whether it be, you know,
verbally or perhaps even unconsciously
convey that to patients and their families.
I'm sure, you know, the process of talking to me,
perhaps they get the impression that this really is going to be...
..a viable...
..potential life-saving option for them.
With Graham, I convey all the potential risks to him
and the fact that it may not work,
and it's just about how far you lead people down that road.
Do I think he came into this with his eyes open?
Maybe you can never have your eyes fully open.
It's easy to distance yourself from these concepts of toxicity.
Sounds like somebody else in some other board in some other hospital.
But I don't dispute the fact
that it's very scary when it's ongoing.
KNOCKING
There is no wire and no mask. No oxygen.
What's happened?
You've performed miracles.
How are you feeling?
I'm coughing up a lot now
which is good, because it means the crap's coming out,
but we're getting there.
The good news is, as you can see, I've got my physio. Oh, yeah.
Game plan for me now is get this chest fixed,
build my strength back up and then get back in the ring
and have another go. Super, super.
That's the plan, so I'm following the instructions.
I've doubled up on what he's asked me to do, then last night,
I actually had the best night's sleep I've ever had. Wow!
I need to get my strength back now
and I'm a bit better.
And I'm eating everything. How's it taste?
It's actually not too bad.
So this is beef lasagne and it actually does taste like lasagne.
Last Friday, I was dying.
Everybody was convinced -
and we're talking about experts here.
Everybody thought, that's it, he's not making it.
I'm still here and I'm still fighting.
And I will not give up.
I just won't.
Graham is very special because he's hugely optimistic.
He's prepared to, like, invest in the, you know,
what the dream outcome is, and he will take
whatever sort of, you know...
I mean, and it's been suffering.
Let's not sort of mince the words around that.
It has been struggling, you know,
the complete existential crisis.
But he's still here.
We just... I feel as if to some extent the boot has been removed
from my neck, you know, in terms of I've been given a little bit
of extra breathing room to try and figure out
what our next moves on the board are.
Primarily, I'm really motivated by data.
I'm not particularly motivated by seeing patients as individuals.
I'm very happy that they do get better,
but what we're really trying to do here
is something that is much bigger than an individual patient.
Directly looking after patients
is always a completely different experience to doing laboratory work.
If you're a scientist, you have to remain objective.
What you don't want to do is make wrong decisions
because you're clouded by emotion.
Think with your head, not with your heart.
You can feel with your heart,
but, you know, you have to think with your head.
There's no point having a super-emotional scientist.
Those individual patients need me to have made
the right design decisions.
And I suppose, to be honest,
there is a certain amount of luck as well.
So you know what's on the cards for this afternoon.
We're going to do that bone marrow test
because you've reached the magic number now.
One whole month since your dose of the Car T cells.
It's quite amazing, isn't it? It's just gone....
It seems it's gone fast for me,
I don't know if it's gone fast for you
lying in the hospital bed this whole time.
I've just been in this room.
I do sympathise, but fingers crossed, right?
Get this bone marrow and then...
..what's next afterwards?
Well, it depends what it shows.
OK.
Mahmoud, wait.
This is clearly a pivotal point for Mahmoud.
He wants to help you hold all of that.
We've seen evidence of Car T cells in his blood.
That's hugely reassuring to me,
and it tells me that the product that we've made, it's got legs,
it's been able to ingraft in Mahmoud.
Whether it's delivered any kind of biological effect, though,
is the big question.
You need to uncover your head.
What are you watching?
Mahmoud.
Yeah? What are you watching.
YouTube.
My name's Clive, I'll be helping to look after you.
My family, we've had our fair share of experience with cancer.
Very close grandfather who developed lung cancer
that was detected very late.
And also my dad, he developed quite an aggressive prostate cancer.
It sort of profoundly changes how you think about illness.
I'm aware of what it's like to be the person on the other side.
Maybe not as nervous as the patient,
but I'm certainly very apprehensive around about these time points.
You don't want to take away anyone's hope.
Hello.
Hello! How are you?
Very quiet and peaceful in here.
Just to say, we have a bit of the marrow results back.
So far, all we have is the fluid bit of the marrow.
But I can say, when we look at it,
we can't see any evidence of disease.
There are no bad cells at all.
Now the reason that we're not sort of jumping up and down
and, well, you know, we have to wait for the solid lump
of the bone marrow, and that gets sent off to the lab
and will take about a week. OK?
Oh, bless her. Oh.
That's so good.
It's really good. I think hopefully, you know,
as Claire was saying, we'll get the rest of it back, yeah?
You all right?
We're really, really...
I mean, we're really hopeful,
but we have to see all the evidence before we can absolutely be sure,
but we are, you know, really happy with that result so far.
Thank you, Claire. Thank you, Ben.
See you later.
What's this...? What?
What's this? Well done.
What's this?
You've done very well. You've been very brave.
OK. OK.
OK. My God.
They have just changed our lives today.
They've lifted the weight on us.
They don't know what they've just done to us.
You OK?
I'm just waiting for next week.
Don't get too hasty.
I think Mum's celebrating too early.
OK.
I'm sorry, I'm not going to celebrate it.
But I'm happy.
That's good.
Graham didn't respond to the first dose of Car T cells.
But we've actually manufactured three doses for him
at the very beginning.
Each dose is higher in terms of cell numbers than the last dose.
He's always had a very positive manner.
And he probably feels under some pressure to stay positive for Mellie
and he's probably trying to stay positive for us,
you know, so that we don't doubt him -
I don't know. Anyways, he's obviously...
..like we all are, you know, complicated characters.
I was hopelessly weak at school with my chest.
If we went on a cross-country run,
I was always the wheezy kid in the back.
The turning point for me was when I was very young
and I went to the doctors and he sat down very kindly
and listed all the things I'd never be able to do in life.
That really messed me up in a way.
In a good way, actually, ironically.
Not in the way he intended.
28, 29...
My father was very supportive,
so what I used to do is I used to go out and try and run on my own
and I went from being the weedy kid at the back
to going to Sandhurst.
Getting commissioned.
I was the first officer we had.
We never failed on anything.
You were saying your dad was good when you were a kid. Yes.
He was a strange man in many ways.
He'd pull up and it would say, "Private wood - keep out."
"Come on. In we go."
"Dad, it says private, keep out."
"Yeah. Not us. That's for other people."
He just used to hate authority.
We'd go and mess around in the woods and stuff
and if - the Duke of Bedford's estate -
if the gamekeeper come over and whatever and said,
"You're not supposed to be in here."
He just used to say, "Fuck off. We're here."
Was he quite heroic to you because of that?
I'm not sure heroic is the right word.
There's a lot of things I'm very grateful for from my father
and there's a lot I'm not grateful for at all.
He was extremely ill - Parkinson's and various other things.
They basically said,
"You're going to be bedridden on morphine all the time."
And...
..he didn't want to do that.
So he used to manage to drag himself out of bed,
drove to the train station,
left my mum a pathetic scrawling
and jumped in front of a train.
And thought he was doing everyone a favour.
Done.
Seems to be the right size so we can get the hand grenade in there.
Hopefully not a hand grenade. Well, it is, mate.
Let's be honest, it's three times the cells this time
so it's going to go with a bang.
OK? So we've got it, it's thawed.
Away we go.
No going back now.
Do you think Graham will be alive in a few months?
Well, you know, I am not God.
If the cells can deliver a kind of response,
he's robust enough, I think, that he'll see it through.
So I look at Graham with the optimism
with which I, you know, have sort of thrown myself 100%
into all the studies. That is that we have to believe
that there is a chance that these will work for him.
Trying to find all your results.
Last week, we had most of them back
but we were just waiting for the most important one for us -
the molecular result.
I am very pleased to be able to say to you
that there is no molecular evidence
of any nasty leukaemia at all anywhere to be seen in that sample.
So does that mean I'm cancer-free?
Absolutely. You are cancer free.
OK. OK. Yeah.
So we're all, like, you know I don't usually get very excited
but I was very excited when I got that piece of information. OK.
We still have some problems.
Your bone marrow is a fairly empty-looking
lonely place at the moment.
You need some red cells, you need some platelets
and you need some neutrophils, all right?
So we have to watch this space.
OK.
Hello. Hello.
Hello, hi. Hi, so I got the news.
OK, what is it?
Are you ready?
Yeah, I'm ready, what is it?
I'm cancer-free.
That is the best news ever.
How do you feel?
I'm OK.
Congratulations!
Thank you.
I can see him.
Hello, Mahmoud. Hello.
You've got your Mahmoud poker face on.
Maybe...
..I'm just a chilled-out person.
Just chilled out.
I think that's true, or under the surface are you less chilled out?
Just on the outside I am chilled out.
What about on the inside?
Very scared.
You've been trying to seem calm for yourself or for others?
One time, when I was starting my treatment for the bone marrow
transplant, after one hour I said to my mum, "I've had enough."
"I don't want to do it any more." Because I was scared.
I told her that and she left work and said she couldn't do it
any more cos she was stressed.
I didn't want to have to make her do that again.
So I kept calm.
I ate food, drink water, just so that never happened again.
She's my best friend.
If you really work your way down to the very core of it,
Martin is the innovator.
His understanding of the biology, and his imagination....
Few other people could have taken us this far.
So I'm told all sorts of good things.
You're looking a lot better than you were this time last week,
and for that I'm really pleased.
Yeah? Yes! At last!
Scientific progress is not an overnight thing.
The Car T-Cell field is built on a huge amount of knowledge that's
been accumulated over the last century.
He should feel more energetic now, doesn't he?
From the understanding of the immune system all the way through to
understanding of the human genome.
It's a lot of hard work.
And also sometimes having some inspirational moments, which often
are disappointing because what you think is an inspirational idea
actually doesn't work.
But occasionally you have a really good idea and it does work.
One of the most important things... KNOCKING
..is not giving up, and being persistent.
Hi. Hi.
Haven't seen you for ages.
You're looking nice, with your little scarf on.
HE CHUCKLES
WATER RUNNING
You're still sitting there looking like the healthiest
sickie on the planet. Well, my red count's gone up.
Platelets have gone up.
Something's happening.
HEART BEATS
Again. And out.
Very, very much improved.
I mean, clearly your charts are just pristine.
And in terms of the Car T cells... Yeah.
..I mean, obviously I haven't had any temperature symptoms yet.
Yeah, yeah. Should I be worried about the fact that it doesn't seem
to have kicked in yet? I don't...
Look, I don't think that there's anything that any of us can do
about whatever's going on. Yeah.
I know it's very hard, but we just need to basically try... Try and put
it out of your head for now. Yeah.
So, on the strength of that, I think there was some sort of tentative
discussion about, go home maybe tonight if everything's OK.
I don't know how you'd feel about that... I'd be delighted to go back.
..maybe weekend leave. Yeah?
I feel a bit lost, really.
We've got no visual symptoms.
But at the same time, the scores are good, so we don't...
We don't really know what's going on.
I don't think THEY do. HE LAUGHS
I don't think they do know what's going on.
Yeah, I mean, how long have you been here now? 73 days.
Be good to get out. I'd quite like to have a glass of wine, actually.
LIFT: Going down.
We've taken Mahmoud through this journey.
It's not been an easy ride for anyone.
To be able to actually send him home to his family,
it's a really special day, for him and also for us.
He realises he's going to be under active surveillance
for months and months.
The US have most data where they've looked at children
up to the age of 18.
They report really high rates of complete response at one month
after treatment - 93% achieving a complete response.
Six months, those numbers have dropped down to about sort of 70%.
If you get to 12 months, 50%, then the chances are
that you will carry on in that way.
There seems to be something about getting to 12 months
where all those survival curves just basically seem to plateau
and you don't tend to see people continuing to fall off.
CHILD SHOUTS EXCITEDLY
You're back!
For him it will be a huge relief to get home, to be in his own bed,
be away from the beeping machines,
and just to be free of us in hospital.
What is it you're wanting to do now that you're home?
I actually don't know what to do now.
Old wind's a bit nippy, actually, isn't it?
Here he is. How we doing?
Have you been down here before, then?
Yeah, we've stayed a few times across at the place
just straight opposite.
There's no TV over there, which is great.
What do you do? I buy wine, actually. Do you? Yeah.
Oh, did you tell me that before? Yes, yeah...
Yeah, last time we were here, but I've been...
I haven't been too well, so we've not been out for a bit.
Oh, right.
You laid up at the moment? Well, I'm just kind of getting over it.
I've had quite a long stay in hospital recently... Yeah?
..so I'm just taking it steady. Yeah.
And what's great about this place is it's, you know,
you've got a lot space, you're not near a load of other people.
Cos I've... My immune system's a bit smashed up. Yeah.
The joys of leukaemia. HE CHUCKLES
We're here and we're having a nice time.
Yeah, we're having a nice time, so...
Right, cheers, then. Cheers, then. Nice to see you. And you.
I love it here.
Ben's back from uni,
and we're trying to do... Steal a couple of days where we can.
I'm really badly smashed up still. My limbs don't work properly yet.
The nerve damage has been quite extensive.
Got a long way to go before I'm back to where it was.
What's down the road, then, in terms of treatment?
They're going to do a bone marrow and see where the treatment's got.
Do you still have faith in the treatment? Yeah, I do, yeah.
I mean, something weird's been going on.
Everybody's very noncommittal, medically, at the minute.
I don't know whether that's a good thing or a bad thing,
but it doesn't matter, really.
At the end of the day it will be what the bone marrow says.
DEEP BREATHING
DRILL BUZZES
HE GROANS
If you wouldn't mind, if you go through the bone marrow results,
just get that done. No, absolutely.
If you're OK with that. I am absolutely fine with that.
All right, so, compared to before
you started this second cycle, you know, there's
much less disease present, but it's not gone.
I'm so sorry.
And any sign of the Car T cells?
Minimal. Is that unexpected or is that... I'm surprised.
I mean, you know, you have to understand that, like, I don't
certainly have all the answers either, but I am surprised
by that. I don't... I can't quite understand it.
And so we have options.
So, either we say the final dose of Car T, the biggest dose
of all might help to kind of like mop up this final
kind of population of cells.
We would do that next week.
Another option is to say if you just don't want to hear
about Car T cells any more, you say, "Right, well, you know, I know
"that I could potentially think about going back on ponatinib."
Recognise that's probably not a long-term solution.
For me, I would want to go with the third dose... Yeah. ..because the
other options that you're describing are really... That's when nothing
else is working.
How's this week been?
Awful.
Really awful.
We had clinic and then we could tell that each other were thinking
things that we didn't really talk about, and then when we got home,
Graham actually got quite angry.
When I was saying, you know, what's best for him and for us as a family,
I was just throwing it out there that maybe the third infusion
isn't the right thing to do.
He just said, "Well, I might as well give up, then - sell my motorbike."
It went from here to just complete nosedive.
Thank you, darling. Tunnock's.
Well, it was good that we had the discussions.
They weren't very nice, between the two us, but...
It's been a difficult week.
But we got there. Yeah.
If I go with the cells next week, it could kill me,
or it could make me seriously ill and, like...
Whatever how long I've got left, I just don't want to waste it
by being in hospital, so I'm not giving up at all.
I'm just being realistic.
And so that's it, done.
We know where we are. And it's not a complete disaster.
It's not as if the trial itself has been wasted.
I mean, they've got some good stuff out from it,
from what's happened with me, that they'll be
able to pass on to the next people.
So in that sense I don't feel that I'm kind of just abandoning
everything. I've... I've done my bit.
Life, for me, is about this.
It's about sitting, the two of us, out here, having a cup of tea.
Eating Tunnock's Teacakes. Eating Tunnock's Teacakes and,
you know, cooking for Amy and Ben,
and just getting on with family life.
It's not about sitting in hospital in green pyjamas.
Yeah, so normal service has been resumed.
Shall we go and have a look at the patch
and see what's growing in there? Yeah.
I don't know whether any of the new stuff has come out.
But there's stuff like that little one there, little ones there.
That's from last year, I think.
There's nothing at this end. Butterfly. Flutterby.
Over the last week or so for Mahmoud, his counts came back and,
at a very low level, we can see
leukaemic cells, which obviously is a massive blow
to even be thinking that's what we can see. The very low level
we are seeing - sort of around two in every 10,000 cells, of healthy
cells - they do look like there's leukaemic cells there.
Please can you not tell him until later?
So he can have a good quality...
..whatever. Yeah.
I know he's 18. I know he's 18, but...
..I would...
As a mother, I know I'll be the one picking up the pieces.
He shouldn't be told, because that will shatter his life.
I don't wish it on a mother.
Watching her son
having treatment, drugs,
medication,
one after the other.
And you're hoping every time he goes through it
and then recovers a bit,
and you're hoping he's going to get better,
and it's not going away.
When a patient relapses, what the tumour sometimes can do is it can
figure out - in an evolutionary sense - what a T-cell is
looking for, and it can decide to switch it off.
So then the T-cell comes along, it's targeting something called
CD19 on the tumour surface, and it kills
99.999% of the tumours.
And one tumour somewhere has a random mutation.
That random mutation switches off CD19,
and now you've got one tumour cell that the Car T-Cell can't see
any more, so the Car T-Cell comes along, finds it and ignores it -
doesn't have CD19 - and then that tumour cell then just starts
dividing and dividing and dividing and takes over the patient.
There's a certain pain that I get when my leukaemia is back,
and I feel it back already.
What is it? It's back pain.
I think this is the last time, cos I can't do any more treatment.
Cos physically and emotionally, I'm extremely limited.
You don't think you could cope with more treatment? No.
So, what, you'd refuse more treatment?
I think I would.
I wouldn't want to do that, because then my sisters, my mum, our family
members won't be able to see me, cos I'll be dead.
Do you worry about the impact on them? I do.
They see their brother every day.
And then he's gone.
Just someone they used to know.
I don't get to control my dreams.
I dream about falling.
When I was younger, I'd just wake up and just run to my mum's bedroom
if I had a scary dream.
It was a reflex.
I'm her first-born.
It'll be very tough to lose someone you've spent so much time with.
How fast is my leukaemia growing?
So, it is coming up quite quickly.
You can see leukaemic cells just down the microscope now.
They are there in very clear numbers, unfortunately, and so
that's what does make it clear-cut.
So it looks like the Car T cells are not able to see
the leukaemic cells, and so they aren't able to attack them, and that
seems to be what has happened.
We are so disappointed about our Car Ts, you know, because we really
were so hopeful that they could get you out of a really
sticky situation,
and it just is the case that the tumour was too smart.
I don't think we're going to be able to get rid of this leukaemia.
You want talk to any friends or anything tonight
about all this? No, it's too hard. No-one understands, do they?
It's not that they don't understand, it's just... It's just too hard to
tell your friend that you're...dying.
To put them in that situation.
I think it's all too much right now, but I think you need to think,
if it was your friend, you'd want to support them, wouldn't you?
I know, but I don't know... How to do that. No.
Oh, it's so nice and sunny. Anyone got Stella?
LAUGHTER Go ahead. I'm going to take my anti-sickness right now.
SCREAMING
Oh, my God! Just look at that!
SCREAMING Holy shit!
How scared were you? It was all right.
Just all right? You didn't cry? No, I didn't cry. HE cried.
HE SCREAMS
I'm not even in there. You can't even... Get in.
Hold on. Look.
CAMERA APP CLICKS
We've known Mahmoud since year three. We've been, like, close
friends, because we played... Remember playing basketball?
He used to be... Yeah, he used to... He used to be good at it. LAUGHTER
End of year eight I met him, yeah. And I was like,
"I want to sit next to this guy." He just had a friendly face.
"I want to sit next to this guy. He looks funny." THEY LAUGH
Cancers are constantly changing,
but they do have an Achilles heel, which is they can't create.
While as conscious engineers we can be much more creative,
and it's through this creativity that we can corner cancers.
I have no doubts that Car T-Cell therapy will work.
We know what problems we need to solve, and we know
how to solve them.
In some ways, the patients in whom the treatment doesn't work
are more important than a patient where the treatment works.
That's really where you can learn the most.
The knowledge that we've gained will then help us to refine our
treatments and hopefully help many hundreds or thousands or millions
of people, ultimately.
I don't know how much families think about that, but that
is something that really should bring them some comfort at least.
ENGINE REVS
I don't think we would ever say we wish we'd never done it, never.
He wanted to be part of making other people better.
Everything starts somewhere.