Ask the Doctor (2017–…): Season 1, Episode 6 - Alcohol - full transcript

[Renee] Genes.

They're the code to who we are
and what makes us unique.

But what happens if that code holds
more information than we bargained for?

Imagine a world where you and your doctor
could access your entire genetic make-up,

and test your predisposition
for hundreds of diseases?

Well, it's closer than you think.

In this episode,
we explore what it could mean

to have health care tailor-made
for each and every one of us.

Sandro reveals a controversial method
that makes it possible to modify our DNA.

We're talking about a tool
with the power to alter the source code

for all life on Earth.



[Renee]
Shalin is faced with an ethical dilemma

when he has the chance to map
his entire genetic make-up.

I don't know that we still
quite understand

what the consequences might be.

[Renee] And I meet Alan,

who owes his young life to the miracles
of these modern discoveries.

[woman] There is a child called Alan,

and if we find out the answers,
we can help him.

[theme music]

[Shalin] From colour blindness
to breast cancer,

diseases with a genetic component

are something we've all learned
to keep a wary eye out for.

As a stem cell scientist,

I'm interested in the role genes play
in a family's health,



especially as I'm yet to have
children of my own.

Now, there's pilot genome sequencing test

that can predict some of the diseases
we are most likely to be predisposed to.

The way it's beginning to be used
has radical implications for health care,

but am I ready for what this test
might tell me?

Associate Professor Marcel Dinger
is one of the leaders in the field,

and heads up Genome. One,

a subsidiary owned by
the Garvan Institute.

He's also a keen oarsman.

Marcel, what excites you
about genomic sequencing?

Well, the ability to be able to read
an individual's entire genetic make-up.

That's pretty amazing.

Once a person has had their DNA sequenced,

it actually makes it possible to tailor
their health care to their DNA.

And this is where it all happens.

[Shalin] The pilot program
taking place in this lab is incredible.

Imagine your body is a library.

Your cells, like tiny bookshelves,

would carry nearly identical books
that contain your genetic instructions.

The chapters would be your chromosomes,

and some of the sentences
would be your genes,

written in the language of your DNA.

If I go through with genome sequencing,

the scientists here would use
the latest technology

to break my code into tiny readable bits.

They'll then put the results back in order

and compare that information to
other people's genetic instructions,

looking for the variants in my gene
that could put me at risk of disease.

But until only recently,

this vast and complex process
used to take much longer.

How long did it take scientists to
sequence a genome 15 years ago?

Almost 15 years,
so that's the extraordinary thing,

is how fast this technology has actually
changed in the last decade or so.

So, on each instrument,

you can sequence about 16
whole human genomes every 3 days.

Across all of the instruments,
about 350 genomes per week.

- Three hundred and fifty a week?
- Yep.

- In this one facility.
- Fifteen thousand a year.

- That's extraordinary.
- Pretty cool, yeah.

Far out. I... I didn't actually...

Honestly didn't realise the scale of that.
Three hundred and fifty a week?

Twenty years ago,

it cost close to a billion dollars
to sequence the very first genome.

Now it costs a few thousand.

If this trend continues,

it could be within everyone's reach
one day.

It's really possible for a human genome
to become part of your medical record,

and that's what really then
makes it possible for a clinician,

I mean, you're, you know,
being seen by a doctor,

that they can actually read information
from your genome

and use that to actually tailor
your health care.

[Shalin] Offering genome sequencing
to healthy people is not without debate.

Critics argue it could make people
worry unnecessarily,

but advocates say it offers people
an informed chance

to be proactive about
looking after themselves.

The biologist in me
wants to do this so bad,

but the consequences
shouldn't be taken lightly.

I'm required to see a genetics counsellor,
so that I can make an informed decision.

We see this pilot as a partnership
between you,

your GP, who's a very important person
in all of this...

- Right.
- ...and us.

Do I get my genome on a CD
I can take home?

[chuckles] Good question.

Um, that's an area that's very, um...

yeah, controversial.

Would you like it?

Probably.

What would you do with it,
just out of interest?

Well, you know, I'd find the software
and look for mutations,

but I know that's, like,
just as bad as being Dr Google.

Now, some people would say that
knowing that information's helpful,

because it assists them
in making life plans.

- Right.
- Other people would say,

"Well, there's nothing you can actually
do about it, medically,

- so I'd prefer not to know."
- Yeah.

So one of the guiding principles
was to test for genes

where you knew that there was something
that you could do about it.

- Right.
- So they call it actionable.

[Shalin] At this centre,
they test for 49 conditions

that could benefit from
medical intervention,

monitoring, or lifestyle changes.

It is a more cautious approach than some.

However, this knowledge still has
potentially negative implications.

With health insurance,
there's actually legislation in place

that protects people
being discriminated against

- on the basis of their genetic make-up.
- OK.

OK? But if you went to take out
a private protective insurance,

- like life insurance...
- Right.

...they would actually ask you,
"Have you ever had a genetic test?"

And they would expect you
to give them the results.

And what you found.
And so, imagine my child grows up,

and his father has a particular mutation
and that's affected my insurance,

will that now affect his insurance
or her insurance?

- Yes, if the laws are still the same.
- Right. Wow.

Yes, yes.
So it is something to think about

in regards to whether or not
you proceed with this test.

- Yeah.
- Yeah.

- Nice to meet you.
- Thanks very much for having me.

- And I'll speak to you in about a week.
- Indeed.

- Bye-bye.
- See you later.

[Shalin] This knowledge is tempting,

but if I am predisposed to
even one of these 49 conditions,

it could affect much more than
just my health.

There's a lot of things
going through my mind right now.

I get the science,

but the other consequences
I'm going to need some time to digest.

I'll talk with my family

and see if I can get some clarity around
whether I'll go through with this.

[Renee] With medical technology
progressing at such a rapid rate,

we asked you... should we be able
to change our genetic make-up

for the health of future generations?

[Shalin] I'm facing one of the
biggest decisions of my life...

should I get my genome sequenced?

It would provide a genetic insight
into my future health,

but bad news could be devastating,

especially if my wife Dimmy and I
choose to have a family.

So, what are you thinking?

I honestly don't know.

I'm... I'm worried a lot.

- But you're not?
- Yeah--

You think I should just do it?

If it were me, I would just do it,

but this is about
what you're comfortable with,

'cause you have to
live with the knowledge.

So, tell me what you're most
concerned about.

I don't know that we still
quite understand

what the consequences might be
for a kid, psychologically,

if I had gene testing, we had a kid,

I knew about the gene that I had,
we didn't do anything about it,

and the kid has a disease
that the genes related to.

And they grow up and they know
we could have done something about it.

- Oh, you're overthinking it.
- No, I'm serious.

Knowing about our genetic make-up
doesn't change our genetic make-up,

but if there's a possibility to do
something about a particular condition,

then I would be pro
finding out and doing it.

I... Yeah, OK.

But you have to be comfortable with
the decision,

so whatever decision you decide,
I'll support.

- You sure?
- Positive.

OK. What if I come back with bad news?

Then we'll deal with it.

[Shalin] It's one thing to consider
the feelings of my imaginary children.

My very real parents need to know as well.

I hope they're home.

But they seem to have been expecting
some other news.

- Hello?
- Are you pregnant?

[both laugh]

No, I'm not pregnant, sorry.

Well, and should you be, we'd be happy.

[Shalin and Dimmy laugh]
- We're just waiting for the news.

So, Mum and Dad,
I need to talk to you about something.

And what is that?

I'm thinking about
getting my genome sequenced.

- OK.
- So, there's a possibility to see

what genes are not quite right
and might cause disease in the future.

Ooh.

Bit scary in a way.

- Good and bad at the same time.
[Shalin] Yeah, yeah.

The ones they're going to look for
are just the ones that,

if there was a problem,

we could potentially
do something about it.

- Uh-huh.
[Shalin] Some cancer,

some cardiovascular disease,
meaning heart attacks and strokes

- and that sort of thing.
- Mm-hm.

And this thing called pharmacogenomics,

which basically means whether I can
metabolise a particular drug or not,

and that can have implications as to
whether a drug is going to work for me

or not going to work for me.

But if I have a faulty gene,

then it came from either you, Mum,
or you, Dad.

So then it also has a consequence for you,

because then you have that gene as well.

Yeah.

Which means one of your siblings
might also have it,

and your nieces and nephews.
So it doesn't just stop with us.

Yeah, but it's also not black and white
with all the genes.

Like, we know that there's
so many things that come into play,

- epigenetics, environment.
- Yeah.

There's so many things
that affect our genes.

There is another theory, also,

that not knowing is better
in few cases as well.

Mm-hm.

Like, too much knowledge is also...

Paralysing, yeah.

What I am saying is you don't have to
depend on what I just said.

You don't make a decision
depending on my statement,

but I am just saying that
it will worry me.

Yeah.

But it also opens the opportunity
to mitigate and do something about it.

I know, I know,
but till it's totally, completely out...

it... it'll...

and I'm sorry,
but I am a worrying type.

You know, so...

[Shalin] My Mum's feelings
have concerned me.

She was a lot more cautious
than I thought she'd be.

- Have a good night.
- Bye. Have a good night.

- Bye, goodnight.
- Bye.

[Shalin] I'm feeling still quite anxious
about the whole thing,

and I think one of the things that's still
stuck in my mind is the ethics of it

and what the future consequences are.

So I'm gonna try and talk to an ethicist
to see what their perspective is,

if there's any unforeseen issues
that I haven't thought about.

- Hi, Lynn, how are you?
- Hi, Shalin.

[Shalin] To get a sounding board
for my concerns,

I'm going to talk with
Professor Lynn Gillam,

who specialises in medical ethics.

She also likes puppies...

[dog barks]

...which I think is why
she's taking me for walkies.

[Lynn] Have a seat here.

One thing I'm worried about is
if I have a faulty gene,

and my wife and I procreate anyway

and that child ends up
getting that disease,

was I unethical in procreating?

Good question. Excellent question.
So, not necessarily.

What you owe your child ultimately is an
explanation for why you did what you did,

but you could have good reasons,

and they might depend on
how bad this fault was,

what other alternatives
there were available.

Right. And then philosophically,
if I have a faulty gene,

then we could conceivably have IVF
and test that embryo,

if it contains that disease,

- and choose to not implant it.
- Mmm.

Are we OK to be "playing God",
inverted commas?

So, playing God is an issue
that people worry about,

but playing God means making choices

about who lives and for how long
and who dies,

and we make those choices all the time,
anyway.

Your decision about when or whether to
have a child is a "playing God" decision.

- So don't get hung up on playing God.
- Right.

- God doesn't mind.
- OK. [laughs]

So, the future's not set in stone,

but ethically,
I feel much more comfortable,

and Lynn's view was basically
what Dimmy was saying all along,

which is no great surprise.

[Dimmy] Hello?
- Hey, it's me.

[Dimmy] Hey.
- Ah, listen, I've come to a decision.

- I'm gonna do it.
[Dimmy] That's great!

Yeah, yeah. OK, I'll speak to you tonight.

[Dimmy] OK, bye.
- Bye.

[woman] So, just a little prick.

[Shalin] Despite the enormity
of the decision,

and what it could mean for my future,

the rest of the procedure
is a simple blood sample.

But the eight weeks I'll have to wait
will be the longest of my life.

[Sandro] Genetics is a field
mined with ethical dilemmas.

We've seen Shalin grapple with
the decision to map his genome,

but what about the ethics
of modifying genes?

It's one of the biggest medical stories
of the 21st century,

and there's a good chance
you haven't heard a single word about it.

It's a set of tools that allow scientists
to modify the genes of any living thing,

accurately, quickly and at low cost.

It's called CRISPR,
but it isn't a machine, or an instrument.

It's actually a group of molecules
that researchers can use like scissors

to target any section of a DNA sequence,
snip it out,

and insert a different piece
of DNA in its place.

It's basically like cutting and pasting,
but for genes.

We're talking about a tool with the power
to alter the source code

for all life on Earth.

CRISPR's being used in labs
across the globe,

with scientists using the technique
to alter cells, viruses,

bacteria, animals and plants,

and they're already achieving
some pretty remarkable stuff.

Including reversing genetic mutations
that can cause blindness,

creating mosquitoes that are
resistant to the malaria parasite.

They've even engineered cells
that are immune to HIV,

the virus that causes AIDS.

But it's important to remember

that all of these results have been seen
in closed lab environments.

Dr Melissa Davis is currently
involved in research

that uses CRISPR to understand

why some cells are more receptive
to cancer treatments than others.

[Melissa] CRISPR is an exciting
new technology,

but there is still potential for defects

that could negative consequences
in patients.

So it's important that we understand these
before we move ahead.

But not all scientists
are showing the same restraint.

In 2016, Chinese researchers
injected CRISPR-modified cells

into a lung cancer patient

in a world-first trial
that's still ongoing,

in order to better understand
the side effects of gene therapies.

And the US is not far behind,

with experimental CRISPR-enabled
cancer treatments

scheduled to start human trials this year.

So it's a brave, if slightly scary,
new world.

But even if scientists are starting to dip
their toes in human CRISPR research,

it's going to be a long time before we see
human gene therapies in common use.

Because, while CRISPR is far more accurate
than tools of the past,

it's nowhere near reliable enough
for human use,

but also because the public's perception
of gene editing

has a long, long way to go.

[Renee] So, the jury is still out

on the ethics of genome sequencing
and genetic editing.

But what if you're sick already
because of your genes?

Professor Chris Goodnow is
Deputy Director of the Garvan Institute,

and head of the Immunogenomics lab.

He also like a gnarly wave.

For him and his team,
the advances in genetic technology

have given them the tools
to not only diagnose and treat

patients with rare illnesses,

but also to bring the technology to them.

Suddenly we could go out to all
the doctors around Sydney and say,

"Look, think about all your really
unsolved cases on your book

where things are not working.

Let's just throw the technology at
the problem and see what comes out."

[Renee]
One case that presented itself was Alan's,

a young boy whose immune system
was attacking his own body.

The symptoms he presented were baffling...

extreme bruising, internal bleeding,

he was also incredibly weak
and losing huge amounts of weight.

He really did have an unusually severe
set of autoimmune conditions,

and none of the conventional medicines
were really helping him.

So what did you guys find
when you did his genome sequence?

So, what we found was that

Alan had inherited a defective copy
of this very large gene

that, up until two years ago,
was a complete mystery gene.

A defective copy from his mother,

and a different defective copy
from his father.

- Wow.
- So just bad luck.

[Renee] Both Alan's copies of this gene
interrupted its function.

They couldn't make the protein needed
to keep immune cells from attacking

and making antibodies
against red cells and platelets.

It was a remarkable find.

Left untreated,
a simple bruise could cause a fatal bleed.

But with Alan's genetic information
at hand,

researchers were able to recommend an
effective treatment in a matter of days.

The start of the weekend,
no-one knew what was wrong with Alan.

At the end of the weekend,
we had this whole package

that we were able to put together.

He very likely would respond to a drug

that was approved for use in people
with other autoimmune disease,

but that you never would have
thought to use.

Yep.

Watching those platelets
and red cells come back,

you know, and Alan going from
being in an intensive care unit, to...

with a very targeted therapy that
was targeted to the right molecule,

based on science, not on guesses...

Alan now has a trampoline
in his front yard,

where previously
he couldn't even run around

for fear of getting a life-threatening
bruise or an internal bleed.

- Boo!
[Renee] Ooh! Hello!

- Hi.
- You must be Alan, are you?

- Yes.
- Do I get to shake your hand?

How are you?
Oh, ooh, you're strong!

To see Alan so energetic
and full of beans,

after what I heard about his illness,
blows my mind.

[laughs] And you must be Burna.
Lovely to meet you too.

But what is living with his condition
actually like

for his parents, Burna and Tansel?

First, imagine you're living with a child
that is not supposed to hit his head,

is not supposed to fall,

and you have to keep an eye on them
24 hours a day.

If he falls, we had to immediately,
you know, take him to hospital,

and that was a bit, you know,
big amount of stress,

because sometimes you'd turn your head
for 30 seconds,

something happens, there's a bump,
and you don't know what happened,

- and you go crazy, basically, so...
[Renee] Yeah.

Grr! Whoa!

Ahh! Oh!

And now?

Now, he runs, he falls,
he gets bruises, we don't care.

[Renee laughs]

Ooh!

Alan seems to have
an unending store of energy.

Whoa!

In fact, I'm having a hard time
keeping up with him.

Whoa!

So, at this point in time,
Alan's not cured, is he?

- No.
- No.

But he's, you know... symptom-free.

[Renee] Despite this improvement,

there's no telling how sustainable
Alan's treatment is long-term.

To try and better understand
his rare condition,

scientists have used the CRISPR technology

to breed mice with the same genetic change
as Alan's.

This means that researchers
can study the condition in isolation

and test new treatments.

Alan has never met
his furry doppelgangers...

You excited?
You're going to meet your mouse!

...but thanks to Dr Debbie Burnett,
that's all about to change.

So, Alan, do you want to meet the mouse?
OK, come on.

So, Alan, these ones here are your mice.

So, these mice were made
specifically for you.

They've got your DNA in them.
Well, some of it. [laughs]

[Renee] Testing treatments on these mice
is essential to Alan's ongoing health.

The technology needed to create them
has been around for a while,

but thanks to CRISPR,

the mice could be bred quickly enough
to help Alan when he was at his sickest.

You know how you were sick before,
and now you're much better?

These mice helped to do that.

Ew, it's pooping!

[laughter]

Ew, yucky.

[Debbie] CRISPR/Cas9
has just changed everything.

It used to take five years
to make a mouse,

and, you know, it was really variable.

I mean, sometimes people spent ages
and they never could.

- Right.
- In this case,

it was a matter of months.
It was real time,

while Alan was in hospital,
that we could make this mouse,

and that's completely changed
the way that we do science,

because right from the beginning,
there was a patient.

I think that's quite rare in science.

Mmm, and how did that make you feel?

It's... It gives everything
a different perspective.

There's a real sense of what's at stake.

It's... You can't forget that
when you're doing this,

knowing that there is not
just people with this disease,

there is a child called Alan
who has this disease

and if we find out the answers,
we can help.

Do you want to name them?

Can you think of a name starting with M?
A "mmm" sound?

- Monana.
- Monana.

Shall we call her Monana? OK.

[laughs]

And so what do you think
this one should be called?

- Mopana.
- Mopana.

- We've got Monana and Mopana.
[Renee chuckles]

Those are possibly the best mouse names
I've ever heard.

- Thank you, Monana.
- [chuckles]

[Renee] It's so gratifying
to see this science applied in real time

and that a child like Alan can have
his whole life turned around

in the space of a week.

In the future,

an ability to pinpoint any genetic problem
with relative ease

may lead to faster diagnosis
of a large range of diseases,

and more appropriate treatments
for everyone.

[giggles]

[Shalin] After eight long weeks,
the day has finally come.

I find out what my genes will tell me
about my medical future.

And I must admit,
there's a growing sense of trepidation.

But I've come this far,
so let's see what they found out.

I'm pretty nervous, but also excited.

Well, maybe what I might start by doing
is just quelling your nerves

and saying there's been no significant
untoward findings in your results.

So the results are normal, alright?
Just as a general statement.

- [exhales]
- Yep.

That's a weight off my shoulders.

OK. So, I just wanted to go through
a little bit about how the test was done.

So we met first,
and then we took your blood sample,

we extracted the DNA
and we put it through the sequencer,

actually analysed it,

and then we've read your genome
from start to finish.

And then what we did was we compared
your genome to a reference genome.

- Mm-hm.
- And we looked for differences.

And you didn't have a variant
that we would call pathogenic

in any of those genes.

I'm good. [chuckles] For now.

OK. Without being a wet blanket,

what we're saying is that
you don't have a high risk

to develop the conditions
associated with these genes.

- Yes.
- You could still develop heart disease,

and you could still develop cancer,
like anyone else in the population.

Because this is just a test for risk.

It doesn't... It's not a...
It's not a crystal ball.

- Correct. Yeah.
- OK.

So let's move on to the
pharmacogenomics report.

[Shalin] I'm so relieved about my results,

I'd almost forgotten that my genes
can also inform how I process drugs.

This drug here is a muscle relaxant.

It could be used, say, if someone gets
spasming with back pain or whatever,

it could be prescribed.

But for you,
it should be used with caution.

Ah, so, OK.

Sorry, I'm just clicking now.

These "use with great caution"
are personalised for me.

- Correct.
- They're not general drugs.

No. They're based on your genotype.

- Wow.
- Yeah.

So I should take this
every time I get a prescription.

Well, it's something
for you and your GP--

- Discuss.
- ...to actually have.

- Fascinating.
- Yeah, yeah, yeah.

So, just thinking about going forward,
part of this,

we will do another reanalysis
in 12 months' time for you.

Because there will be
additional medications

that will be added to this list,

as well as additional genes
that we'll be able to test for.

- So it's an evolving process.
- Correct.

These are the genes you know about now
and how they...

- how drugs will interact with my biology.
- Yep.

- But that list will grow over time.
- Yep.

Right, so it's getting the latest
operating system on your computer.

Yes.

You just do an update, check again.
"Oh, yeah."

Yeah, you make it sound easy.
It's not quite that easy. [laughs]

I'm sure it's not that easy.

I know for a fact from my science life
that it's not easy.

Well, that was quite
a remarkable experience.

Now, I can understand genome sequencing
is not for everyone,

as there are some potential issues
and repercussions.

As a scientist, I see the power
of genomic information every day,

but to see it informing me and my health
was quite extraordinary.

Keeping in mind
we're still in uncharted territory,

I'm really excited to see
where this goes in the future.

[Renee] There is so much about genes
that we're yet to understand,

but the science and technology
are not only here, they're changing lives.

While we're still determining what role
environment plays in our make-up,

and the ethical boundaries
this field presents...

it's incredible to think
that we might one day

be able to plug our genome
into a doctor's computer

and have specifically targeted
health care

not just for ourselves,
but also for our future generations.

And that will be good news for everyone.