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Good evening.

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Above my head is a threat...

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..a bucket of gunge.

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And there is a 50-50 chance that,

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when the counter runs out of time,
I'm going to get hit.

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Should I take the risk?

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Or should I protect myself?

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AUDIENCE: Four, three, two, one...

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APPLAUSE

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Welcome.

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Welcome to the 2021 Christmas
lectures from the Royal institution.

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I'm Professor Jonathan Van-Tam

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and I'm the Deputy Chief Medical
Officer of England.

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But tonight, I'm actually talking
to you as a

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respiratory virus epidemiologist.

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Now, last time, we explored how
viruses like coronaviruses

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can exploit human interactions
to spread across the globe,

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causing damage to people,
to families and to societies.

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And we really want to know,
how can we fight back?

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Now the umbrella was a bit
like a vaccine.

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It's a hidden defence system that
you can take everywhere with you.

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And perhaps vaccines
against Covid-19 have been

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the biggest scientific achievement
of the last two years.

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In the past, making a vaccine was
a lengthy process -

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up to 20 years, in fact.

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So it's a pretty ground-breaking
accomplishment, and a testament

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to the quality of modern science,
that we have

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come so far that we can develop
vaccines in under 12 months.

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So what are they
and how do they work?

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To reveal the incredible science
of vaccines, our first expert

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this evening is one of
the developers

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of the Oxford-AstraZeneca vaccine.

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Would you please welcome
Professor Teresa Lambe.

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I'm a vaccine scientist,
and for a long time I have been

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researching and making vaccines
against diseases like Ebola and flu.

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When SARS-CoV-2 came along,
hundreds of other scientists

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just like me dropped everything.

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We pulled together all
the knowledge we had,

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our expertise, to create
a vaccine...

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..and it worked.

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So how did we do it?

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Well, our knowledge of vaccines
and how they work isn't new.

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It's built on centuries
of scientific progress

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and human knowledge.

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And it stretches back around
500 years, to China.

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Back then, smallpox plagued
human civilisation and had done

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so for thousands of years.

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Here we have poor Nick.

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He's got the classic symptoms
of smallpox -

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they're not pleasant at all.

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He's got horrible pustules
all over his skin that would

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turn into scabs, and these were
filled with highly infectious virus.

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Smallpox killed about 30%
of those it infected.

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And it was common.
It is estimated to have

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killed around 300 million
people in the last century alone.

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But people began to notice that
if you survived

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smallpox infection, you would not
suffer from the disease again.

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You would be immune,

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you would be protected against
catching smallpox a second time.

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Physicians at this time
took this knowledge

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and tried to achieve protection
in a more controlled way.

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To see the process they came up
with, I need a volunteer.

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Yes, you, come on down,
in the grey top.

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Hello, what's your name? Alliya.
Alliya, thank you.

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So, Alliya, can you just stand
over here for me?

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And if you just face this way, don't
look at the pustules just yet,

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they're a bit too gross.
Thank you, Alliya.

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So what I want you to do is,
I want you to peel off

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some of these smallpox scabs.

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So you've got a forceps there
and I want you to peel them off

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and put them into here.

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It's why I wanted a volunteer.

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LAUGHTER

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So scabs were chosen carefully.

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They wanted scabs from people
with mild, weak disease,

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believing that they would be safest.

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Great job.

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Now, if you could grind them up.

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Grind them up?!
Yeah, give it a good bash.

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Perfect.

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So the next step is to get those
ground-up scabs into somebody,

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to give them the immunity to
protect them from smallpox.

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And one method of getting those
scabs into a person

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involved a nose.

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That's why we've got it here.

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So just wait one second.

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So what I'm going to ask
you to do...

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..is suck some of the scabs
up into this, OK?

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Uh...

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Just give it a bit of a suck.

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Great, now follow me over here.

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All the way around.

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And if you can put it all the way up
the nostril, that would be great.

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And on the count of three,
give it a big puff, OK?

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Three, two, one, go!

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And that's how we got smallpox
scabs into people 500 years ago.

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Thank you so much for your help.

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APPLAUSE

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So what do you think happens if you
take the scabs from somebody

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else's skin, grind them up
and put them in someone's nose?

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Do they get ill?

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Well, absolutely, they do get ill.

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And these people would become
infected and sick with smallpox.

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But if they recovered,
they would develop immunity.

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And, believe it or not, many people
wanted this protection

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back in the day.

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Because about 30% of people
who got smallpox

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from a wild infection were dying.

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But it was still a pretty
risky procedure.

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And when people practised
this in Europe,

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it killed around 2% of people
who had the treatment.

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So although it was far safer than
catching smallpox naturally,

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it's not the kind of risk that we
would be willing to take today.

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And it was not until the 1700s
that a safer alternative emerged.

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And that alternative involved a man
called Edward Jenner...

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..a milkmaid...

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..and a cow.

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LAUGHTER

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APPLAUSE

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Here we have Sarah, the milkmaid,

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and Blossom, the cow.

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They were actually their real names.

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These pustules on Sarah's
hands are from Blossom,

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who was infected with a disease
called cowpox.

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It looks nasty for poor Blossom
and Sarah.

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Growing general knowledge
at the time had demonstrated that

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milkmaids like Sarah, who'd been
infected with cowpox, were

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immune to the much more deadly
disease smallpox.

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Jenner clocked onto this
and started to experiment.

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JVT, would you like to be Jenner?
I certainly would.

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What Jenner did was take a sample
of the pustules from Sarah's

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hands with a syringe.

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I'm going to step back from this.

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Come over here, Sarah.

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I've got to suck up some of
the pus from your hands here.

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Oh, that's lovely. Oh.

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Thank you very much, Sarah.

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Then he injected the pus
under the skin

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of a healthy young boy called James.

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Do we have anyone
called James in the house?

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Up there, at the top, in the white
shirt - come on down.

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So, James, it's your lucky day.

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You didn't know it, but I'm going
to take some of Sarah's pus

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and inject it into your hand.

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This shouldn't hurt.

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LAUGHTER

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James suffered a fever.

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He was ill for nine days,
but he recovered.

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And two months later, Jenner
exposed James to the far more deadly

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disease of smallpox,
but James was immune.

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This was an incredible discovery.

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Jenner had shown a way to gain
immunity from smallpox,

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but in a much safer way.

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And in honour of Blossom the cow,
Jenner called the technique

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vaccination, because vacca
is cow in Latin.

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Thank you, Blossom.

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APPLAUSE

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OK, OK, Blossom, don't milk it.

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All right, that's enough,
off you go.

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Thank you, Blossom, thank you,
Sarah, thank you, James.

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Thanks, James.

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APPLAUSE

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Most people wanted to become
vaccinated to protect

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themselves from smallpox,
but some people were suspicious.

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This cartoon shows some of the views
at the time.

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Some people believed that
vaccination might actually

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turn you into a cow.

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Fortunately, this has not happened -

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no-one has turned into a cow
from vaccination.

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Over time, vaccines continued to
be developed to combat other

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deadly diseases, too,

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with huge levels of success.

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So, let's see some of the diseases
that vaccines have fought.

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And here we have
the diphtheria vaccine.

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Now, before we had vaccination,
in England and Wales alone,

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there were 50,000 cases
of diphtheria a year.

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And after it...

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Only one!

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What have we got next?

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So here...

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..I've got the measles vaccine.

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And again, in England and Wales
before we had measles vaccines,

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there were 460,000 cases each year.

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And afterwards?

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Just 130.

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And finally, we've got a really
horrible one here, of course -

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smallpox. And for this one,
we've really got to

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talk about the whole world,
because it was a scourge.

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And a mid-20th century estimate...

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..was that 15 million cases
of smallpox occurred every

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year around the world, and that
caused five million deaths.

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Do you know how many cases
of smallpox there are each

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year in the world now?

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MANY: Zero.

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OK, so some quite low numbers
and some zeros in there.

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You got it, the answer is zero.

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APPLAUSE

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In 1980, the horrific disease
smallpox that had plagued

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humanity for thousands of years
was declared eradicated.

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All because of global
vaccination programmes.

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And this was an incredible
achievement of science.

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Like all medicines, there can
be some unwanted

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side-effects from vaccines.

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And for a tiny, tiny fraction
of the population,

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these can be significant.

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But really, the probability is
incredibly low and, when you weigh

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the risks against the benefits,
the evidence and the data are clear.

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And, in fact, only one thing
has ever saved more lives

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in human history than vaccines...

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..and that is clean water.

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To understand how vaccines work,
we need to understand how viruses

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infect us and how our
immune system works.

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Like we've seen before in these
lectures, let's think

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of the cells in our body
as a factory.

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Imagine everything inside here
is the inside of a cell.

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But outside of the cell is
SARS-CoV-2, the coronavirus.

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Boo!

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AUDIENCE BOOS

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On the outside of the virus,
you can see lots of the famous

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00:14:00,200 --> 00:14:02,040
spike protein.

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The spike protein acts like a key,
helping the virus

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get into our cells.

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Oh, no, you're in!

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AUDIENCE BOOS

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Once the coronavirus
is inside of our cell,

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it needs to copy itself,
so what happens now?

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Here is its genetic material.

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And here is the boss' office,
the cell nucleus,

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where your DNA is kept,
our genetic material.

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Some viruses can actually
break into the boss' office,

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but Covid doesn't do that - it goes
straight to our cell factory

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machinery, the ribosome.

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The ribosome is really important
at making things like proteins

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that our body needs.

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Covid hijacks the ribosome

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and inserts its genetic code to
make copies of itself.

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WHIRRING

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Unfortunately, what this means
is the virus has won.

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So we've had a lot of fun with that,
but there's a serious point.

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We've shown how viruses can
get into our cells

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and copy themselves and make
us sick.

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So it's our immune system's job to
stop this from happening.

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Unlike in Jenner's time,

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we now know our immune system
is made of an army of things,

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like antibodies from T-cells
and killer T-cells that can

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attack viruses and stop them
in their tracks.

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And, as we've seen, the immune
system protects us really well

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when it already remembers what
the disease looked like,

249
00:15:42,040 --> 00:15:45,600
either from a previous
infection or a vaccination.

250
00:15:45,600 --> 00:15:48,800
So let's see our immune system's
memory on this board here.

251
00:15:48,800 --> 00:15:50,840
It's already got some
viruses on there.

252
00:15:51,840 --> 00:15:54,800
This is measles, which you'll have
seen either through

253
00:15:54,800 --> 00:15:57,680
vaccination or have been exposed.

254
00:15:57,680 --> 00:16:00,720
So you know how to recognise
it and fight it off.

255
00:16:00,720 --> 00:16:04,840
This one is HPV, it's a nasty virus
that increases the risk

256
00:16:04,840 --> 00:16:09,120
of cervical cancer, for which
there is an amazing new vaccine.

257
00:16:09,120 --> 00:16:12,120
But what about SARS-CoV-2?

258
00:16:12,120 --> 00:16:14,760
Well, if we get infected
and recover,

259
00:16:14,760 --> 00:16:16,880
we will have some
immunity to the virus.

260
00:16:16,880 --> 00:16:20,720
Our immune system will remember it,
but we want a vaccine to

261
00:16:20,720 --> 00:16:24,640
train our immune system without
us getting infected.

262
00:16:24,640 --> 00:16:26,800
So how do we do this?

263
00:16:26,800 --> 00:16:29,880
Well, let's look at some of the ways
that vaccines have been developed

264
00:16:29,880 --> 00:16:32,560
to fight Covid-19.

265
00:16:32,560 --> 00:16:34,320
LAUGHTER

266
00:16:34,320 --> 00:16:37,640
Where do you want this, love?
Anywhere but on my toes, JVT.

267
00:16:39,160 --> 00:16:40,400
There you go.

268
00:16:41,720 --> 00:16:46,080
One method is to take the whole
virus...

269
00:16:46,080 --> 00:16:48,200
..but inactivate it.

270
00:16:50,800 --> 00:16:54,600
So to inactivate it, we heat it up,
we cool it down,

271
00:16:54,600 --> 00:16:56,240
we mix it with some detergents.

272
00:16:56,240 --> 00:16:59,840
A bit like putting
it in a washing machine.

273
00:16:59,840 --> 00:17:03,560
And that makes the virus no
longer infectious.

274
00:17:03,560 --> 00:17:05,000
WASHING MACHINE WHIRS

275
00:17:05,000 --> 00:17:07,760
So it's a no-longer-functioning
virus.

276
00:17:12,880 --> 00:17:15,120
Ooh. Oh.

277
00:17:15,120 --> 00:17:16,560
LAUGHTER

278
00:17:18,360 --> 00:17:20,480
It may be a
no-longer-functioning virus,

279
00:17:20,480 --> 00:17:22,440
but it does still look like it.

280
00:17:22,440 --> 00:17:23,880
Yeah.

281
00:17:23,880 --> 00:17:28,440
So these whole inactivated vaccines
are used to vaccinate people,

282
00:17:28,440 --> 00:17:31,920
to train our immune system
to recognise the virus,

283
00:17:31,920 --> 00:17:33,640
to keep us safe.

284
00:17:33,640 --> 00:17:36,800
So it's ready to attack the minute
it sees the virus,

285
00:17:36,800 --> 00:17:39,080
if it ever tries to get in.

286
00:17:39,080 --> 00:17:41,560
And this is the whole
inactivated vaccine method.

287
00:17:41,560 --> 00:17:46,080
It's only one in a plethora of
methods we have for making vaccines.

288
00:17:46,080 --> 00:17:49,760
Inactivated vaccines are one
of the most commonly used vaccines

289
00:17:49,760 --> 00:17:51,760
to combat Covid-19.

290
00:17:51,760 --> 00:17:55,960
And they're used frequently in
countries like China and Brazil.

291
00:17:55,960 --> 00:17:57,800
There's the virus, get it!

292
00:18:07,360 --> 00:18:10,680
Well protected, immune system,
you've done your job.

293
00:18:10,680 --> 00:18:12,840
You've kept us safe from Covid.

294
00:18:12,840 --> 00:18:15,560
But there's a bit of a mess here.

295
00:18:15,560 --> 00:18:17,920
JVT? Hm.

296
00:18:17,920 --> 00:18:18,920
LAUGHTER

297
00:18:20,520 --> 00:18:22,160
Put your back into it.

298
00:18:25,200 --> 00:18:27,280
So that's one type of vaccine,

299
00:18:27,280 --> 00:18:30,240
but there are other ways to
make vaccine.

300
00:18:30,240 --> 00:18:32,440
Instead of helping our
immune systems

301
00:18:32,440 --> 00:18:35,920
to recognise the whole virus,
some vaccines work by targeting

302
00:18:35,920 --> 00:18:38,120
just a small piece of the virus.

303
00:18:39,320 --> 00:18:43,680
For SARS-CoV-2, one of those pieces
is the famous spike protein.

304
00:18:43,680 --> 00:18:46,840
I helped co-design an
adenoviral-vectored vaccine,

305
00:18:46,840 --> 00:18:49,680
known as the Oxford-AstraZeneca
vaccine,

306
00:18:49,680 --> 00:18:52,320
but there are other types of
vaccines just like this,

307
00:18:52,320 --> 00:18:54,520
known as Janssen or J&J.

308
00:18:54,520 --> 00:18:57,360
Let's see how these viral-vectored
vaccines are made.

309
00:18:57,360 --> 00:18:59,200
For this, I need a volunteer.

310
00:19:00,640 --> 00:19:02,800
First-hand up that I saw.

311
00:19:08,680 --> 00:19:11,920
Hi, what's your name?
My name's Max. Max.

312
00:19:11,920 --> 00:19:14,440
So instead of starting with
the coronavirus,

313
00:19:14,440 --> 00:19:16,800
we're going to start with something
called a viral vector.

314
00:19:16,800 --> 00:19:20,280
It's still a virus, but it's
modified to be harmless.

315
00:19:20,280 --> 00:19:23,480
So let's put this coat on and make
you into a viral vector.

316
00:19:25,360 --> 00:19:28,440
The viral vector is called
an adenovirus.

317
00:19:28,440 --> 00:19:30,200
Now, the clever part.

318
00:19:30,200 --> 00:19:35,080
We swap a small part of the
adenovirus' genetic code

319
00:19:35,080 --> 00:19:37,920
and we give it the crucial
instructions, the recipe,

320
00:19:37,920 --> 00:19:42,360
if you will, to make the
coronavirus' famous spike protein.

321
00:19:42,360 --> 00:19:44,640
So I'm going to give you this
and I'm going to take

322
00:19:44,640 --> 00:19:46,960
a little bit away from you.

323
00:19:50,240 --> 00:19:53,480
And that's it, we've got
our vaccine.

324
00:19:53,480 --> 00:19:56,120
So when we inject
viral-vector vaccine,

325
00:19:56,120 --> 00:19:59,560
it tries to do what viruses do -
it tries to make copies of itself,

326
00:19:59,560 --> 00:20:03,320
but it can't be because we've
modified the adenovirus.

327
00:20:03,320 --> 00:20:08,200
It can only make copies of the spike
protein using the ribosome.

328
00:20:08,200 --> 00:20:10,720
So if you go over to the ribosome,

329
00:20:10,720 --> 00:20:13,960
and you put your spike
protein in...

330
00:20:17,880 --> 00:20:19,840
..what comes out?

331
00:20:19,840 --> 00:20:23,440
Thousands and thousands of copies
of the spike protein.

332
00:20:23,440 --> 00:20:26,080
Thank you so much, Max,
you've done your job.

333
00:20:26,080 --> 00:20:28,960
APPLAUSE

334
00:20:30,280 --> 00:20:34,440
So the cell has made thousands
of copies of the spike protein.

335
00:20:35,760 --> 00:20:39,560
And our immune system has now seen
the spike protein

336
00:20:39,560 --> 00:20:42,840
and we've made an immune memory
against the spike protein.

337
00:20:45,720 --> 00:20:49,480
So we're ready to attack the
virus when we see it,

338
00:20:49,480 --> 00:20:51,160
attacking the spike protein.

339
00:20:52,560 --> 00:20:55,920
That's vaccine number two,
the viral-vectored vaccine.

340
00:20:57,560 --> 00:21:01,920
And that vaccine number two has
already saved hundreds

341
00:21:01,920 --> 00:21:05,000
and thousands of lives
around the world.

342
00:21:06,080 --> 00:21:12,400
So, Tess, how did it feel when you
realised that vaccine had worked?

343
00:21:12,400 --> 00:21:14,720
It felt like we all needed
a bit of a sit down

344
00:21:14,720 --> 00:21:18,480
because there'd been an awful lot of
work. But, no, it felt fantastic.

345
00:21:18,480 --> 00:21:22,560
The whole team had worked tirelessly
for many, many months,

346
00:21:22,560 --> 00:21:26,640
trying to make an impact, trying to
help us get out of this pandemic.

347
00:21:26,640 --> 00:21:29,880
So it was a fabulous feeling.
Thank you.

348
00:21:29,880 --> 00:21:34,520
So there is a third
method of making a vaccine

349
00:21:34,520 --> 00:21:37,360
and it's a really very
revolutionary one.

350
00:21:37,360 --> 00:21:41,160
It's called M, or messenger
RNA vaccines.

351
00:21:41,160 --> 00:21:44,160
And they go by the tradenames
of Pfizer and Moderna

352
00:21:44,160 --> 00:21:47,920
at the moment, so some of you
will recognise them.

353
00:21:47,920 --> 00:21:50,600
But actually, in terms
of principles,

354
00:21:50,600 --> 00:21:54,080
it's a really simple vaccine.

355
00:21:54,080 --> 00:21:58,800
It is just a piece of RNA,
that's all.

356
00:21:58,800 --> 00:22:03,160
But, somehow, it has to get into
the cell safely.

357
00:22:03,160 --> 00:22:04,680
And for that...

358
00:22:05,800 --> 00:22:08,480
..you have to wrap it up...

359
00:22:10,080 --> 00:22:15,760
..in a package so that it can
get into the cell nice and safely.

360
00:22:15,760 --> 00:22:20,040
And, usually, that piece of RNA
is wrapped in a package

361
00:22:20,040 --> 00:22:22,280
of fats and lipids.

362
00:22:22,280 --> 00:22:24,520
It sounds really easy, doesn't it?

363
00:22:25,880 --> 00:22:29,400
But, actually, just to get to this
stage took decades

364
00:22:29,400 --> 00:22:31,520
and decades of research.

365
00:22:31,520 --> 00:22:34,440
And our next expert can tell
us a lot more

366
00:22:34,440 --> 00:22:36,880
about messenger RNA vaccines.

367
00:22:36,880 --> 00:22:40,160
So please put your hands together
and welcome Dr John Tregoning.

368
00:22:46,040 --> 00:22:49,040
John, tell us really how this
special package works.

369
00:22:49,040 --> 00:22:52,520
OK, so the RNA vaccines are trying
to do exactly the same

370
00:22:52,520 --> 00:22:55,360
thing as all the other vaccines,
which is target the coat

371
00:22:55,360 --> 00:22:59,240
of the virus and stop it getting
into our cells and taking over.

372
00:22:59,240 --> 00:23:02,920
But what the RNA vaccines do is take
a very small component,

373
00:23:02,920 --> 00:23:06,040
the spike, and just
the RNA of that spike.

374
00:23:06,040 --> 00:23:09,560
And the trick behind them is, they
have a special modified RNA

375
00:23:09,560 --> 00:23:13,200
which has been changed to make the
protein factory of the cells

376
00:23:13,200 --> 00:23:16,720
make more copies of that spike,
better priming our immune system

377
00:23:16,720 --> 00:23:18,720
to fight off the virus.

378
00:23:18,720 --> 00:23:21,080
But the other thing that's
helped them work so well is,

379
00:23:21,080 --> 00:23:24,240
that envelope you're holding
protects the RNA and

380
00:23:24,240 --> 00:23:27,000
gets it into the cell better
so you can make more copies.

381
00:23:27,000 --> 00:23:29,320
So there's bits of technology
in there that have

382
00:23:29,320 --> 00:23:31,200
helped the vaccine work much better.

383
00:23:31,200 --> 00:23:34,680
So was I really right when
I said it's all rather simple?

384
00:23:34,680 --> 00:23:36,720
No, not really.

385
00:23:36,720 --> 00:23:39,120
There's been decades of research
that have gone into this.

386
00:23:39,120 --> 00:23:41,880
What we're seeing in the last
two years is really

387
00:23:41,880 --> 00:23:45,360
the end of a 20-year programme
of vaccine research.

388
00:23:45,360 --> 00:23:48,120
And what we're doing is building
on the soldiers of giants

389
00:23:48,120 --> 00:23:50,640
like Jenner, and hopefully maybe
laying the foundation

390
00:23:50,640 --> 00:23:52,760
for people like you in the audience,
that you can build

391
00:23:52,760 --> 00:23:54,640
the next generation of vaccines.

392
00:23:54,640 --> 00:23:59,360
I've got to ask, if that coronavirus
pandemic had come along

393
00:23:59,360 --> 00:24:02,840
five years ago, or ten years ago,

394
00:24:02,840 --> 00:24:06,680
would the messenger RNA vaccine
technology have been ready?

395
00:24:06,680 --> 00:24:08,640
So, no, I don't think so.

396
00:24:08,640 --> 00:24:11,360
I think we learnt a lot from
the Ebola pandemic,

397
00:24:11,360 --> 00:24:13,480
or outbreak, in the 2010s.

398
00:24:13,480 --> 00:24:16,240
And that taught us that the way
that we develop vaccines

399
00:24:16,240 --> 00:24:20,720
is not quick enough to deal with
a rapidly moving viral pandemic.

400
00:24:20,720 --> 00:24:23,640
And this led to change in the ways
that we think about vaccines

401
00:24:23,640 --> 00:24:25,440
and the way that we develop them.

402
00:24:25,440 --> 00:24:28,280
All of it building on years
of research but just changing

403
00:24:28,280 --> 00:24:30,720
the speed at which it can be done.

404
00:24:30,720 --> 00:24:34,000
Thank you, John, that's absolutely
fascinating, thank you.

405
00:24:39,080 --> 00:24:42,720
So tonight you've seen three very
different ways

406
00:24:42,720 --> 00:24:46,080
of making a Covid-19 vaccine.

407
00:24:46,080 --> 00:24:49,320
And the fastest of those
techniques gave us

408
00:24:49,320 --> 00:24:55,640
a vaccine that was developed
in just 326 days.

409
00:24:55,640 --> 00:24:59,040
That is a world record and it also
beats the previous

410
00:24:59,040 --> 00:25:03,600
record of four years by a very
considerable margin.

411
00:25:05,240 --> 00:25:09,840
But the goal for the future
is to go even faster.

412
00:25:09,840 --> 00:25:14,640
And next time we need a new vaccine,
for Covid and possibly

413
00:25:14,640 --> 00:25:18,920
other diseases too, to get one
in just 100 days.

414
00:25:20,600 --> 00:25:23,040
But getting a vaccine recipe...

415
00:25:24,360 --> 00:25:28,320
..is just the start of a much
bigger challenge.

416
00:25:29,960 --> 00:25:35,880
The question is, how do you get from
one vaccine in a researcher's lab,

417
00:25:35,880 --> 00:25:40,400
to 12.5 billion doses

418
00:25:40,400 --> 00:25:44,000
projected to be produced by the end
of one year?

419
00:25:44,000 --> 00:25:47,560
Because that's what we're heading
for at the moment, as we come

420
00:25:47,560 --> 00:25:50,160
towards the end of 2021.

421
00:25:50,160 --> 00:25:53,920
And the answer is,
scientific expertise,

422
00:25:53,920 --> 00:25:57,520
industrial expertise and teamwork.

423
00:25:57,520 --> 00:26:00,480
This is a vaccine factory at work.

424
00:26:00,480 --> 00:26:05,360
It requires thousands of factory
workers, truck drivers,

425
00:26:05,360 --> 00:26:09,320
engineers and health care workers.

426
00:26:09,320 --> 00:26:12,360
And there's a huge
amount of material resources

427
00:26:12,360 --> 00:26:13,960
going in there, too.

428
00:26:13,960 --> 00:26:17,640
Rubber stoppers,
glass vials, packaging.

429
00:26:19,120 --> 00:26:22,800
And there's even a problem at the
other end, if you make all

430
00:26:22,800 --> 00:26:27,360
these vaccines and you don't
have the fridges to store them in.

431
00:26:27,360 --> 00:26:31,680
Some vaccines can actually be
stored in fridges,

432
00:26:31,680 --> 00:26:34,520
just like the ones you have at home
in your kitchens.

433
00:26:35,600 --> 00:26:38,680
But others need much colder
temperatures to keep

434
00:26:38,680 --> 00:26:40,640
some of these vaccines stable.

435
00:26:40,640 --> 00:26:44,040
And a particular one are the
messenger RNA vaccines,

436
00:26:44,040 --> 00:26:46,040
which are very fragile.

437
00:26:46,040 --> 00:26:51,160
They require temperatures of
minus 62 to 80 degrees Celsius

438
00:26:51,160 --> 00:26:55,360
in order to keep that messenger
RNA stable.

439
00:26:55,360 --> 00:26:58,600
And for those kind of really
cold temperatures,

440
00:26:58,600 --> 00:27:01,160
we need lots of this stuff...

441
00:27:01,160 --> 00:27:03,160
..dry ice.

442
00:27:07,120 --> 00:27:12,560
And then, once the vaccines get out
there to the health centres,

443
00:27:12,560 --> 00:27:17,440
they still need to be administered
and put into people's arms.

444
00:27:17,440 --> 00:27:20,920
And for that we need a different
kind of army, of health care

445
00:27:20,920 --> 00:27:25,560
workers and volunteers -
an absolutely huge effort.

446
00:27:25,560 --> 00:27:30,360
And at the time of recording this
show, a week before Christmas,

447
00:27:30,360 --> 00:27:36,880
nearly 125 million vaccines have
been given out across the UK.

448
00:27:38,160 --> 00:27:43,120
It is the biggest vaccination
programme the UK has ever run.

449
00:27:43,120 --> 00:27:47,160
But vaccinating the UK
is really only a small

450
00:27:47,160 --> 00:27:49,800
part of the global task.

451
00:27:49,800 --> 00:27:53,600
And until we are all protected
across the world,

452
00:27:53,600 --> 00:27:57,440
then I'm afraid to say
none of us are truly safe.

453
00:27:58,640 --> 00:28:00,280
APPLAUSE

454
00:28:03,520 --> 00:28:05,760
The beauty of science is that
all the knowledge

455
00:28:05,760 --> 00:28:09,600
we have learned through Covid
we can use for other diseases, too.

456
00:28:09,600 --> 00:28:15,120
Viruses and diseases like Ebola,
Zika, flu and even HIV.

457
00:28:15,120 --> 00:28:19,360
And vaccines have even been
trialled to kill cancer.

458
00:28:19,360 --> 00:28:22,080
To see how this vaccine
treatment could work,

459
00:28:22,080 --> 00:28:25,600
let's start by looking
at our genetic code.

460
00:28:25,600 --> 00:28:30,440
Unfortunately, sometimes
parts of our DNA can change.

461
00:28:31,480 --> 00:28:34,360
This means that some
proteins can change

462
00:28:34,360 --> 00:28:37,160
and our cells can
grow uncontrollably.

463
00:28:37,160 --> 00:28:39,480
A cell has become cancerous.

464
00:28:40,880 --> 00:28:43,640
Once we know what has
changed in this protein

465
00:28:43,640 --> 00:28:47,440
we can make a vaccine to help
our immune system see the protein,

466
00:28:47,440 --> 00:28:52,480
recognise it, kill the cancer cells
and eradicate the cancer.

467
00:28:52,480 --> 00:28:56,200
And in this way, we'll be able
to make vaccines that can attack

468
00:28:56,200 --> 00:28:58,840
and help protect us against cancer.

469
00:28:58,840 --> 00:29:01,400
So who wants to attack a cancer
cell?

470
00:29:01,400 --> 00:29:04,120
You at the back,
with the yellow sleeves.

471
00:29:04,120 --> 00:29:05,480
Come on down.

472
00:29:05,480 --> 00:29:07,280
APPLAUSE

473
00:29:11,920 --> 00:29:13,640
Hi, what's your name? Oscar.

474
00:29:13,640 --> 00:29:15,800
Oscar, hello, lovely to meet you.

475
00:29:15,800 --> 00:29:20,240
You're going to be a killer
T-cell, a destroyer of cancer.

476
00:29:20,240 --> 00:29:24,160
So what I need you to do is first
of all put on these goggles.

477
00:29:25,480 --> 00:29:27,800
And then I need you to go
over to Matt

478
00:29:27,800 --> 00:29:30,880
and then put on these
ear defenders, OK?

479
00:29:30,880 --> 00:29:33,920
So I need everybody in the audience
to put your hands

480
00:29:33,920 --> 00:29:37,160
over your ears - this is going
to be super loud.

481
00:29:37,160 --> 00:29:38,800
OK, hands over ears.

482
00:29:39,880 --> 00:29:41,640
Everybody ready?

483
00:29:41,640 --> 00:29:44,360
Three, two, one...

484
00:29:44,360 --> 00:29:46,240
LOUD BANG

485
00:29:46,240 --> 00:29:48,520
APPLAUSE

486
00:29:51,720 --> 00:29:55,480
Thank you so much, Oscar.
You've killed a cancer cell,

487
00:29:55,480 --> 00:29:58,200
you are a destroyer of cancer,
you can take your seat.

488
00:29:58,200 --> 00:29:59,640
Well done.

489
00:29:59,640 --> 00:30:02,080
APPLAUSE

490
00:30:05,000 --> 00:30:08,720
So we've shown you how vaccines
train the immune system

491
00:30:08,720 --> 00:30:13,440
to recognise threats before
they even arrive.

492
00:30:13,440 --> 00:30:17,720
And also how in the future
they could be used to help

493
00:30:17,720 --> 00:30:22,880
our immune systems to fight
diseases such as cancer.

494
00:30:22,880 --> 00:30:27,360
So vaccines are primarily
protective measures,

495
00:30:27,360 --> 00:30:31,840
but they also have the potential
to cure in the future.

496
00:30:34,320 --> 00:30:36,800
Tess, what are you working
on these days?

497
00:30:36,800 --> 00:30:39,320
SARS-CoV-2 is still keeping
me up at night.

498
00:30:39,320 --> 00:30:41,960
We're still looking at the
immune system, looking to see

499
00:30:41,960 --> 00:30:44,640
how we can combat variants
of concern.

500
00:30:44,640 --> 00:30:47,400
We've also found a little time
to work on new vaccines,

501
00:30:47,400 --> 00:30:49,080
vaccines against Ebola.

502
00:30:49,080 --> 00:30:50,280
Fantastic.

503
00:30:50,280 --> 00:30:52,760
Well, I wish you all the best with
that work, thank you so much

504
00:30:52,760 --> 00:30:56,680
for joining us all this evening to
explain all about vaccinology.

505
00:30:56,680 --> 00:30:58,280
Thank you so much, JVT.

506
00:30:58,280 --> 00:31:00,840
APPLAUSE

507
00:31:03,640 --> 00:31:06,920
So we're now in a golden
age of vaccines.

508
00:31:08,120 --> 00:31:13,720
Knowledge and progress that helped
develop Covid-19 vaccines

509
00:31:13,720 --> 00:31:18,920
in this record time have now served
to kind of turbo-charge

510
00:31:18,920 --> 00:31:21,520
our future ambitions in this area.

511
00:31:22,880 --> 00:31:25,920
But the pandemic is not over yet.

512
00:31:25,920 --> 00:31:30,520
We are now seeing the rise
of the Omicron variant.

513
00:31:30,520 --> 00:31:36,000
Viruses have this final trick up
the sleeve, that they can mutate.

514
00:31:36,000 --> 00:31:38,400
And one of the reasons why
we have been

515
00:31:38,400 --> 00:31:43,320
so successful in tracking
the Omicron variant

516
00:31:43,320 --> 00:31:48,640
is because the UK is an absolute
world leader

517
00:31:48,640 --> 00:31:55,160
in genetic sequencing, that's given
us that ability to track the virus.

518
00:31:55,160 --> 00:32:00,800
And to reveal the science of viral
variants and the mysteries

519
00:32:00,800 --> 00:32:04,640
of genomics, would you please
welcome Professor Sharon Peacock.

520
00:32:04,640 --> 00:32:07,720
APPLAUSE

521
00:32:11,680 --> 00:32:14,160
So thank you and hello.

522
00:32:14,160 --> 00:32:17,840
I'm a microbiologist and my job
during the pandemic

523
00:32:17,840 --> 00:32:21,720
has been to generate the genetic
code of the SARS-CoV-2 virus

524
00:32:21,720 --> 00:32:25,880
to keep tabs on how
the virus is changing.

525
00:32:25,880 --> 00:32:31,280
And we can see how important that is
right now with the Omicron variant.

526
00:32:31,280 --> 00:32:33,480
So to understand how we get
variants,

527
00:32:33,480 --> 00:32:37,240
we need to talk about genomes
and genetic mutations.

528
00:32:37,240 --> 00:32:41,200
We're not talking about mutants
or comic book superheroes

529
00:32:41,200 --> 00:32:42,880
with superpowers.

530
00:32:42,880 --> 00:32:46,080
No, all organisms on the planet
change over time

531
00:32:46,080 --> 00:32:49,800
when random mutations occur in their
genetic code.

532
00:32:51,320 --> 00:32:53,800
So this is a model of DNA.

533
00:32:55,200 --> 00:32:58,040
It's a famous double helix.

534
00:32:58,040 --> 00:33:01,080
It's made up of two chains
that coil around each other

535
00:33:01,080 --> 00:33:05,320
and it carries the genetic code,
the recipe, that makes you you,

536
00:33:05,320 --> 00:33:07,240
and me me.

537
00:33:07,240 --> 00:33:11,760
And that code is contained in nearly
every cell in our body.

538
00:33:13,080 --> 00:33:16,640
So each chain contains four
different nucleotides

539
00:33:16,640 --> 00:33:20,920
and we refer to them
as A, C, G and T.

540
00:33:20,920 --> 00:33:23,160
So imagine a string of letters

541
00:33:23,160 --> 00:33:25,240
here in my spinner is a tiny

542
00:33:25,240 --> 00:33:27,680
part of one of these DNA strands.

543
00:33:31,200 --> 00:33:34,920
So when our cells replicate,
the exact code is copied

544
00:33:34,920 --> 00:33:40,200
but there is a chance that a copying
error occurs, like a typo,

545
00:33:40,200 --> 00:33:43,200
and another letter is
introduced by mistake.

546
00:33:44,680 --> 00:33:48,440
So in human cells, the chances
of mutation is really very small

547
00:33:48,440 --> 00:33:51,280
indeed, it one in a billion times
that a cell divides.

548
00:33:52,360 --> 00:33:54,840
But we're going to use this
spinner today to see

549
00:33:54,840 --> 00:33:57,200
if we can spot a change.

550
00:33:57,200 --> 00:33:59,400
Now, take a look at the letters
of the spinner.

551
00:33:59,400 --> 00:34:03,040
And as I start to turn the handle,
which is our simple model

552
00:34:03,040 --> 00:34:06,920
of the DNA copying itself,
I need you to help me.

553
00:34:06,920 --> 00:34:08,880
So shout out if you see a change.

554
00:34:10,720 --> 00:34:12,680
MANY: Change.

555
00:34:12,680 --> 00:34:14,560
OCCASIONAL SHOUTS

556
00:34:16,600 --> 00:34:17,960
ALL: Change! Yes!

557
00:34:17,960 --> 00:34:19,680
Yes, there's a change.

558
00:34:21,200 --> 00:34:24,400
Change!
That's brilliant, thank you.

559
00:34:24,400 --> 00:34:28,000
Now, for humans it's really good
that genetic mutation

560
00:34:28,000 --> 00:34:30,080
is very, very slow.

561
00:34:30,080 --> 00:34:33,600
Mutations can make us sick -
that's how cancers can arise.

562
00:34:34,960 --> 00:34:36,920
But what about viruses?

563
00:34:36,920 --> 00:34:41,360
Now, SARS-CoV-2 and some other
viruses, such as influenza,

564
00:34:41,360 --> 00:34:46,320
carry their genetic code not
in DNA, but in something called RNA.

565
00:34:46,320 --> 00:34:49,520
Now, RNA has a different code
and structure to DNA

566
00:34:49,520 --> 00:34:53,840
and we refer to it using letters
A, C, G and U.

567
00:34:54,880 --> 00:34:58,160
Now these viruses are genetic
gamblers and up to a million

568
00:34:58,160 --> 00:35:02,320
times more likely to mutate
themselves in our own body.

569
00:35:03,440 --> 00:35:05,440
So let's go back to our spinner.

570
00:35:06,600 --> 00:35:11,840
Change. Change.

571
00:35:11,840 --> 00:35:15,440
Yeah, there's a fair amount of
change there, isn't there?

572
00:35:15,440 --> 00:35:16,920
Yep, one more.

573
00:35:16,920 --> 00:35:19,440
Change!
Yes, change, thank you.

574
00:35:19,440 --> 00:35:25,000
So viruses are the fastest
evolving organisms on the planet.

575
00:35:25,000 --> 00:35:27,000
And each time a virus code
is copied,

576
00:35:27,000 --> 00:35:30,400
there's a chance that a genetic
error is introduced.

577
00:35:30,400 --> 00:35:32,840
Now when you think about infection
in a human,

578
00:35:32,840 --> 00:35:36,920
the virus is copying itself
millions of times, and millions

579
00:35:36,920 --> 00:35:41,040
of people are being affected around
the world with SARS-CoV-2.

580
00:35:41,040 --> 00:35:43,200
So there's a lot of chances
to mutate,

581
00:35:43,200 --> 00:35:44,680
but why does it matter to us?

582
00:35:44,680 --> 00:35:47,800
Well, every small change in the
genetic code can have a big

583
00:35:47,800 --> 00:35:50,320
effect on how the virus behaves.

584
00:35:50,320 --> 00:35:54,360
One possible change is that the
virus can alter in such a way

585
00:35:54,360 --> 00:35:58,400
that it becomes more difficult for
our immune system to recognise it.

586
00:35:58,400 --> 00:36:02,640
And that's important because it's
there to fight off infection.

587
00:36:02,640 --> 00:36:05,520
So we are going to see how the
competition between variants

588
00:36:05,520 --> 00:36:09,840
and our immune system works with
help from some furry friends,

589
00:36:09,840 --> 00:36:14,080
which you can see on our screen,
keenly waiting outside.

590
00:36:14,080 --> 00:36:15,360
AUDIENCE: Aw.

591
00:36:15,360 --> 00:36:18,880
They're lovely, aren't they?
Look at them. Beautiful.

592
00:36:18,880 --> 00:36:23,080
So our dogs are playing the parts
of viral variants.

593
00:36:23,080 --> 00:36:26,480
Each dog is playing the part
of a different viral variant.

594
00:36:26,480 --> 00:36:30,480
The cage is our cells, and variants
want to get inside of our cells

595
00:36:30,480 --> 00:36:33,800
to cause an infection. And if
you're a dog, you get some lovely

596
00:36:33,800 --> 00:36:35,520
treats if you get inside.

597
00:36:35,520 --> 00:36:38,920
But playing the part of our
immune system is this special

598
00:36:38,920 --> 00:36:41,680
recognition system
right here on this screen.

599
00:36:42,880 --> 00:36:45,320
It's been trained to recognise
a generic dog,

600
00:36:45,320 --> 00:36:50,440
a bit like a vaccine works, but
does it recognise all variant dogs?

601
00:36:50,440 --> 00:36:54,000
So who will win out in the end,
the variant or our immune system?

602
00:36:55,240 --> 00:37:00,200
Here is our first viral variant,
being played by Poppy.

603
00:37:00,200 --> 00:37:02,760
Isn't she lovely?

604
00:37:02,760 --> 00:37:05,440
So, Poppy's really keen
to get inside the cage

605
00:37:05,440 --> 00:37:07,760
and get those treats.

606
00:37:07,760 --> 00:37:11,960
So let's see if the immune system
recognises the variant,

607
00:37:11,960 --> 00:37:13,400
let's see what happens.

608
00:37:13,400 --> 00:37:14,800
ALARM BLARES

609
00:37:14,800 --> 00:37:16,040
Oh, I'm really sorry,

610
00:37:16,040 --> 00:37:17,080
Poppy, but look...

611
00:37:18,320 --> 00:37:21,400
..you were recognised by the immune
system, and out you go.

612
00:37:21,400 --> 00:37:22,800
AUDIENCE VOICE DISCONTENT

613
00:37:24,560 --> 00:37:27,200
Poppy failed to get past
the cage defences.

614
00:37:27,200 --> 00:37:31,480
Not good for the dog, but good for
us because our immune system worked.

615
00:37:31,480 --> 00:37:35,520
But what about dog variant
number two?

616
00:37:35,520 --> 00:37:37,200
This dog looks very different

617
00:37:37,200 --> 00:37:39,280
from Poppy -
perhaps they're faster -

618
00:37:39,280 --> 00:37:44,160
but how effective will our immune
system be against Luciano?

619
00:37:44,160 --> 00:37:47,320
So do you think variant two
will get the treats?

620
00:37:47,320 --> 00:37:49,560
Yes. You do? You do think?

621
00:37:49,560 --> 00:37:53,760
OK... No. No? We've got a yes
and a no, so let's see, shall we?

622
00:37:56,000 --> 00:37:57,800
ALARM BLARES

623
00:37:57,800 --> 00:37:59,040
Oh, no.

624
00:37:59,040 --> 00:38:02,040
No, our immune system has worked
again and that viral variant

625
00:38:02,040 --> 00:38:05,400
hasn't got into our cell. So thank
you very much and bye-bye, Luciano.

626
00:38:08,880 --> 00:38:12,680
OK, right, our next variant
is played by Mr Fluffy.

627
00:38:13,920 --> 00:38:17,400
He looks very different from other
dogs, and so will Mr Fluffy

628
00:38:17,400 --> 00:38:19,000
get past the recognition system

629
00:38:19,000 --> 00:38:20,880
and get the treats?
AUDIENCE: Aw!

630
00:38:20,880 --> 00:38:23,480
What do you think - will he get
through? Will he get through?

631
00:38:23,480 --> 00:38:24,880
Yes or no?

632
00:38:24,880 --> 00:38:26,760
MIXED RESPONSE

633
00:38:26,760 --> 00:38:29,040
Oh, really, really mixed.

634
00:38:29,040 --> 00:38:32,800
We'd quite like him to get the
treats, but let's see what happens.

635
00:38:32,800 --> 00:38:35,240
Oh, well done.

636
00:38:35,240 --> 00:38:37,880
There you go, Mr Fluffy,
you get the treats,

637
00:38:37,880 --> 00:38:41,560
and there's quite a lot
there for you to eat.

638
00:38:41,560 --> 00:38:44,960
So the variant is different
enough to avoid

639
00:38:44,960 --> 00:38:46,960
recognition of our immune system.

640
00:38:46,960 --> 00:38:50,400
He got past our immune system
and we will be infected.

641
00:38:50,400 --> 00:38:55,000
It's good for Fluffy, particularly
as he's got so much chicken,

642
00:38:55,000 --> 00:38:58,560
but really bad for us
because we've become infected.

643
00:38:58,560 --> 00:39:02,160
So thank you very much to Mr Fluffy.

644
00:39:02,160 --> 00:39:05,520
And I'm really sorry, Mr Fluffy,
but you're going to have to go.

645
00:39:11,000 --> 00:39:12,720
DOG BARKS

646
00:39:13,880 --> 00:39:15,720
That dog didn't get the chicken.

647
00:39:15,720 --> 00:39:17,080
MULTIPLE BARKS

648
00:39:18,760 --> 00:39:22,760
So, you know, this is a lot of fun
but there's a really serious point

649
00:39:22,760 --> 00:39:26,480
to Mr Fluffy's success, because
variants really matter to us.

650
00:39:27,640 --> 00:39:30,280
Because they can get past our
immune system and variants

651
00:39:30,280 --> 00:39:33,760
are something we have to monitor
very closely with Covid-19.

652
00:39:35,720 --> 00:39:38,080
If a virus variant becomes
more transmissible,

653
00:39:38,080 --> 00:39:41,760
it could spread more quickly
and cause more cases.

654
00:39:41,760 --> 00:39:45,680
Variants could also make us more
unwell if we're infected.

655
00:39:45,680 --> 00:39:48,520
Unlike we saw just now, variants
may start to evade our immune

656
00:39:48,520 --> 00:39:53,440
system defences, and these are what
we call variants of concern.

657
00:39:53,440 --> 00:39:56,360
Dodging our immune system is
the worry with Omicron.

658
00:39:57,640 --> 00:40:00,480
So, JVT, can you give us
a quick update on Omicron?

659
00:40:02,200 --> 00:40:06,560
Right now, at the time of recording,
a week before Christmas,

660
00:40:06,560 --> 00:40:10,080
there's a lot we don't know
about Omicron.

661
00:40:10,080 --> 00:40:15,400
But what we can say is that it is
already growing very, very fast

662
00:40:15,400 --> 00:40:18,160
in the UK, and it will have grown
some more

663
00:40:18,160 --> 00:40:21,280
by the time this programme
goes out on the air.

664
00:40:22,640 --> 00:40:27,880
And that's despite many of us
already having been vaccinated.

665
00:40:27,880 --> 00:40:34,160
And it seems like this variant
is partially dodging the vaccine.

666
00:40:34,160 --> 00:40:38,400
And that's why it's making it
really important for adults

667
00:40:38,400 --> 00:40:43,600
to have a booster dose, and
early data is now beginning to show

668
00:40:43,600 --> 00:40:47,080
that this is going to reduce
the risk of being infected.

669
00:40:49,520 --> 00:40:51,880
Thank you very much, JVT.

670
00:40:51,880 --> 00:40:56,040
So, let's take a look at
what is changing with this virus.

671
00:40:56,040 --> 00:40:59,440
Let's zoom in on the spike protein,
which decorates the outside

672
00:40:59,440 --> 00:41:03,960
of the coronavirus, to see how much
it has changed over time.

673
00:41:03,960 --> 00:41:07,040
So we're going to look at
this image here.

674
00:41:07,040 --> 00:41:11,960
So, these show the spike proteins
of three different variants.

675
00:41:11,960 --> 00:41:16,400
On the left is the original virus
that first emerged.

676
00:41:16,400 --> 00:41:20,400
The middle is the Delta variant
that's still circulating among us

677
00:41:20,400 --> 00:41:22,880
and across much of the world
at the moment.

678
00:41:22,880 --> 00:41:26,880
But this is the spike protein
for Omicron.

679
00:41:27,920 --> 00:41:29,760
Now, you can see how different
they are,

680
00:41:29,760 --> 00:41:35,400
and the red and the blue indicates
where the spike protein has changed.

681
00:41:35,400 --> 00:41:40,200
Now, Omicron has around 50 different
mutations in the entire genome

682
00:41:40,200 --> 00:41:42,160
compared with the early virus

683
00:41:42,160 --> 00:41:45,960
and around 30 concentrated
in that spike gene.

684
00:41:45,960 --> 00:41:47,280
Now, that's a lot of change.

685
00:41:47,280 --> 00:41:51,520
And it means that the spike looks
different to our immune system.

686
00:41:51,520 --> 00:41:54,720
And it's so different that
this is why we're being asked

687
00:41:54,720 --> 00:41:58,320
to get a booster,
to increase our immunity.

688
00:41:58,320 --> 00:41:59,800
So how do we keep track of variants?

689
00:41:59,800 --> 00:42:03,280
Well, everything really hinges on
having the complete genetic code

690
00:42:03,280 --> 00:42:07,640
of the virus or its genome,
and this comes down to huge advances

691
00:42:07,640 --> 00:42:11,760
in genetic sequencing technology
over the last 30 years.

692
00:42:11,760 --> 00:42:14,840
So, let's take a look at
how far we've come.

693
00:42:18,680 --> 00:42:20,320
Now, 20 years ago,

694
00:42:20,320 --> 00:42:22,200
the Human Genome Project
was finished

695
00:42:22,200 --> 00:42:25,240
and we decoded the DNA of a human.

696
00:42:25,240 --> 00:42:26,840
So, see the result here -

697
00:42:26,840 --> 00:42:32,320
118 hardback books containing over
three billion base pair letters.

698
00:42:32,320 --> 00:42:36,960
Now, the cost was £2 billion
and it took 13 years to complete.

699
00:42:36,960 --> 00:42:39,520
Ten years ago, the cost of
sequencing a human genome

700
00:42:39,520 --> 00:42:41,680
had dropped to £38,000.

701
00:42:41,680 --> 00:42:45,200
And now, as technology
has got more automated,

702
00:42:45,200 --> 00:42:49,200
the human genome can be sequenced
for under £400.

703
00:42:49,200 --> 00:42:54,000
And now we get the chance to see
just how simple it is to do.

704
00:42:56,200 --> 00:42:57,960
APPLAUSE

705
00:43:02,160 --> 00:43:05,120
Here we have Kim Judge
from the Wellcome Sanger Institute.

706
00:43:05,120 --> 00:43:08,520
And she'll be showing us
the latest sequencing technology.

707
00:43:08,520 --> 00:43:11,440
So, Kim, can you tell us
what you're going to show us today?

708
00:43:11,440 --> 00:43:15,000
Sure. So, here we have
a hand-held sequencing device.

709
00:43:15,000 --> 00:43:18,160
And we can use this to sequence
the genome of SARS-CoV-2.

710
00:43:18,160 --> 00:43:21,040
Oh, so that's safe, is it?
Completely safe, yes.

711
00:43:21,040 --> 00:43:22,720
We've prepared it in a lab earlier,

712
00:43:22,720 --> 00:43:24,440
there's no longer
a virus present,

713
00:43:24,440 --> 00:43:26,240
it's just genetic material. OK.

714
00:43:26,240 --> 00:43:28,120
So can you show us
what you're going to be doing

715
00:43:28,120 --> 00:43:30,000
to set up the machine
to sequence? Sure.

716
00:43:30,000 --> 00:43:33,040
So I've already input some details
about what we're going to be doing

717
00:43:33,040 --> 00:43:36,400
onto the touch screen here.
I'm going to open this up.

718
00:43:36,400 --> 00:43:39,960
And we have a small hole that
we can pipette the DNA into.

719
00:43:39,960 --> 00:43:44,000
So this is the pipette. I'm just
going to give it a little mix.

720
00:43:44,000 --> 00:43:46,560
Just move it up and down
a bit like that.

721
00:43:46,560 --> 00:43:48,920
And then, with a very steady hand,

722
00:43:48,920 --> 00:43:50,600
just squirt it on here.

723
00:43:53,560 --> 00:43:58,200
So...once we've done that,
we can close it all back up again.

724
00:43:58,200 --> 00:44:01,000
It's just going to take a couple of
moments to sort of drink

725
00:44:01,000 --> 00:44:05,800
the liquid in, and then we can press
this button here for start.

726
00:44:05,800 --> 00:44:09,800
That's amazing, isn't it, that
you can sequence in this theatre?

727
00:44:09,800 --> 00:44:11,840
That simply is quite extraordinary.

728
00:44:11,840 --> 00:44:14,600
But I know it's going to take a few
minutes to get going. That's right.

729
00:44:14,600 --> 00:44:17,760
And you've brought another machine
that's just slightly further ahead,

730
00:44:17,760 --> 00:44:22,200
so we can actually see some of
the sequence data being read out.

731
00:44:22,200 --> 00:44:25,040
That's correct. So, we've got one
here that's been running

732
00:44:25,040 --> 00:44:27,320
for just a few minutes already.

733
00:44:27,320 --> 00:44:29,400
So what you can see here
is, actually,

734
00:44:29,400 --> 00:44:32,400
those green boxes represent
the genetic code,

735
00:44:32,400 --> 00:44:36,120
including the mutations that might
suggest that this is a variant.

736
00:44:36,120 --> 00:44:37,800
Indeed. Yeah.

737
00:44:37,800 --> 00:44:40,920
I mean, the fact that this is
such a small piece of kit means

738
00:44:40,920 --> 00:44:42,480
that you could take it anywhere.

739
00:44:42,480 --> 00:44:45,360
And I wonder if you can tell us
the most exciting place

740
00:44:45,360 --> 00:44:47,160
it's been used to
sequence something.

741
00:44:47,160 --> 00:44:49,840
I mean, there's quite a few places
it's been, but I think

742
00:44:49,840 --> 00:44:52,600
the coolest place, probably,
is the International Space Station.

743
00:44:52,600 --> 00:44:56,120
That is pretty cool, actually.
OK, well, thank you for coming, Kim.

744
00:44:56,120 --> 00:44:59,160
Thank you very much. Thank you.
APPLAUSE

745
00:45:01,960 --> 00:45:05,240
So, something that is really
unprecedented during the pandemic

746
00:45:05,240 --> 00:45:08,920
is we have generated more than
5.5 million SARS-CoV-2 genomes

747
00:45:08,920 --> 00:45:10,720
around the world.

748
00:45:10,720 --> 00:45:13,560
We monitor tiny changes
in the virus's genetic code

749
00:45:13,560 --> 00:45:16,120
in close to real time as possible.

750
00:45:16,120 --> 00:45:18,840
Now, pathogen genomics has actually
never been able to do this

751
00:45:18,840 --> 00:45:21,200
on this scale or speed before.

752
00:45:22,960 --> 00:45:25,480
So we can see the advantages of this
for Omicron.

753
00:45:25,480 --> 00:45:27,440
Genomic scientists
and vaccine scientists

754
00:45:27,440 --> 00:45:30,280
are working very closely together
as a team.

755
00:45:30,280 --> 00:45:33,040
And the genetic code of Omicron,
identified last month

756
00:45:33,040 --> 00:45:37,520
on 23 November, was fed through
to vaccine makers.

757
00:45:37,520 --> 00:45:41,560
And they've been working on
new vaccines specific to Omicron.

758
00:45:41,560 --> 00:45:46,040
They predict they could be ready to
vaccinate us in just 95 days.

759
00:45:46,040 --> 00:45:49,280
And this is staggeringly fast.

760
00:45:49,280 --> 00:45:52,000
So, we can merge all of
our genomic information

761
00:45:52,000 --> 00:45:54,720
to build up a vast virus
family tree,

762
00:45:54,720 --> 00:45:58,680
which you can see on this screen,
for the United Kingdom.

763
00:45:58,680 --> 00:46:03,560
Now, each colour that you see
represents a viral variant,

764
00:46:03,560 --> 00:46:07,000
and you can see over the course
of the two years of the pandemic

765
00:46:07,000 --> 00:46:10,040
how that's changed over time.

766
00:46:10,040 --> 00:46:12,280
Now, in the first part
of the pandemic,

767
00:46:12,280 --> 00:46:16,320
you can see there's a great deal
of different variants,

768
00:46:16,320 --> 00:46:19,240
none of which are really
outcompeting the other.

769
00:46:19,240 --> 00:46:21,920
So, through random mutation
and natural selection,

770
00:46:21,920 --> 00:46:25,000
perhaps one will win the jackpot
because it's more competitive

771
00:46:25,000 --> 00:46:27,760
than the other. This is like
a fitness race.

772
00:46:27,760 --> 00:46:30,920
And this is what happened
when Alpha emerged.

773
00:46:30,920 --> 00:46:34,520
So, on the green here, you can see
Alpha becoming very dominant

774
00:46:34,520 --> 00:46:35,880
in the population.

775
00:46:37,040 --> 00:46:39,520
Here, you can see that Delta
then emerged

776
00:46:39,520 --> 00:46:42,760
and actually outcompeted Alpha.

777
00:46:42,760 --> 00:46:45,440
And right at the very far part
of the chart here,

778
00:46:45,440 --> 00:46:48,640
you can see - in red - Omicron.

779
00:46:48,640 --> 00:46:50,760
Now, that looks very small
at the moment,

780
00:46:50,760 --> 00:46:55,000
but actually this chart only goes
up to the beginning of December.

781
00:46:55,000 --> 00:46:58,880
And what we're predicting is that,
by Christmas or into the new year,

782
00:46:58,880 --> 00:47:03,320
that red will go right the way up
and become dominant,

783
00:47:03,320 --> 00:47:05,240
as the dominant variant.

784
00:47:05,240 --> 00:47:07,400
So we need to expect much more
from this variant,

785
00:47:07,400 --> 00:47:09,720
and what we need to celebrate,
in fact,

786
00:47:09,720 --> 00:47:12,240
is that we've got eyes
on the virus all of the time

787
00:47:12,240 --> 00:47:15,240
in a way that we really never
have achieved before.

788
00:47:15,240 --> 00:47:17,480
And that's a very good thing for us.

789
00:47:20,040 --> 00:47:23,320
If these viruses keep hitting
the jackpot,

790
00:47:23,320 --> 00:47:28,840
then will we continue to see these
further changes in the future?

791
00:47:28,840 --> 00:47:32,520
Well, I'm sure that SARS-CoV-2 has
got a few more tricks up its sleeve.

792
00:47:32,520 --> 00:47:36,160
I think we're going to see
more variants actually emerging.

793
00:47:36,160 --> 00:47:40,040
I think a really important question
is whether it will mutate itself

794
00:47:40,040 --> 00:47:43,400
out of fitness, because only so many
changes in the genetic code

795
00:47:43,400 --> 00:47:45,280
can really be managed together

796
00:47:45,280 --> 00:47:48,000
before the virus starts to lose
its fitness.

797
00:47:48,000 --> 00:47:51,240
So, in the end, it's possible that
the virus will become

798
00:47:51,240 --> 00:47:54,240
like the common cold,
nothing more serious than that,

799
00:47:54,240 --> 00:47:56,720
but we haven't really reached
that point yet.

800
00:47:56,720 --> 00:47:59,680
So we just have to stay vigilant
until we get there,

801
00:47:59,680 --> 00:48:01,200
because we don't know the future?

802
00:48:01,200 --> 00:48:05,440
Yeah. Absolutely vigilant. And we've
got the technology to do that now.

803
00:48:05,440 --> 00:48:08,840
How does it feel to be part
of that big effort?

804
00:48:08,840 --> 00:48:11,840
Well, it's really amazing
to have been in the right place

805
00:48:11,840 --> 00:48:14,120
at the right time.
And just a few years ago,

806
00:48:14,120 --> 00:48:17,040
we wouldn't have been able
to provide this vital information

807
00:48:17,040 --> 00:48:20,320
in the pandemic response,
and so that's incredible.

808
00:48:20,320 --> 00:48:23,240
I would say, though, that we've
achieved this through the work

809
00:48:23,240 --> 00:48:26,400
of a great many people, so I pay
tribute to all of those people

810
00:48:26,400 --> 00:48:29,720
that have helped us. So, pathogen
genomics is really here to stay.

811
00:48:29,720 --> 00:48:31,720
We can use it to fight
future pandemics

812
00:48:31,720 --> 00:48:34,120
and we can also use it
for other threats,

813
00:48:34,120 --> 00:48:37,040
such as antibiotic resistance.

814
00:48:37,040 --> 00:48:40,800
How far, where could we actually go
with genetic sequencing in the end?

815
00:48:40,800 --> 00:48:43,120
What we could do is defied by
my own imagination,

816
00:48:43,120 --> 00:48:46,640
because we are currently sequencing
all of life on Earth.

817
00:48:46,640 --> 00:48:48,160
We can sequence our own genome,

818
00:48:48,160 --> 00:48:50,680
we can sequence the microorganisms
in and around us,

819
00:48:50,680 --> 00:48:54,680
we can sequence in hospitals,
clinics, the jungle, in space.

820
00:48:54,680 --> 00:48:58,280
And I find it very difficult
to imagine what that will lead to.

821
00:48:58,280 --> 00:49:00,800
But, actually, I think
it will provide new information

822
00:49:00,800 --> 00:49:05,760
to help humans stay healthier and
actually help preserve our planet.

823
00:49:05,760 --> 00:49:08,600
Sharon, thank you so much
for showing us

824
00:49:08,600 --> 00:49:11,040
inside the world of genomics
this evening.

825
00:49:11,040 --> 00:49:13,680
You've been fantastic.
Thank you very much, JVT.

826
00:49:19,760 --> 00:49:22,840
So you've seen that the secrets
to success

827
00:49:22,840 --> 00:49:28,840
might lie in the genetic code.
And it raises a question.

828
00:49:28,840 --> 00:49:33,280
Through that, can we be
better prepared for the future

829
00:49:33,280 --> 00:49:39,000
and could part of that better
preparation come from finding

830
00:49:39,000 --> 00:49:44,760
where these viruses actually
come from in the first place?

831
00:49:44,760 --> 00:49:48,880
So if we trace back to
the very earliest variants

832
00:49:48,880 --> 00:49:54,840
of this coronavirus pandemic, we can
actually start to gather some clues

833
00:49:54,840 --> 00:49:57,720
about where it might have come from.

834
00:49:57,720 --> 00:50:01,840
And there are some possible hints
that lead back

835
00:50:01,840 --> 00:50:06,280
to a most remarkable creature -
the bat.

836
00:50:07,320 --> 00:50:10,040
And I'd like to welcome David King.

837
00:50:10,040 --> 00:50:12,080
APPLAUSE

838
00:50:15,920 --> 00:50:20,520
And if you look carefully on the
screen, David has a bat with him.

839
00:50:21,920 --> 00:50:25,240
David, what species of bat
do we have here?

840
00:50:25,240 --> 00:50:30,680
This is a pipistrelle, which is
the smallest of 17 British species.

841
00:50:30,680 --> 00:50:35,200
Despite its small size -
it only weighs 5g,

842
00:50:35,200 --> 00:50:39,280
which is the same weight
as a 20p piece -

843
00:50:39,280 --> 00:50:41,880
it can live 15 years

844
00:50:41,880 --> 00:50:47,880
and each night it can consume
3,000 mosquito-sized insects.

845
00:50:47,880 --> 00:50:49,800
Can you tilt it towards the camera?

846
00:50:49,800 --> 00:50:54,440
So, David, is it safe to have a bat
in here, in the lecture theatre?

847
00:50:54,440 --> 00:50:56,760
It's trying to escape
all the time, obviously,

848
00:50:56,760 --> 00:50:58,760
because it's not
a natural environment,

849
00:50:58,760 --> 00:51:03,960
but it is safe because it's
a captive bat that has been rescued

850
00:51:03,960 --> 00:51:07,440
because it was injured
or abandoned as a baby,

851
00:51:07,440 --> 00:51:09,400
so it's not a good flyer.

852
00:51:09,400 --> 00:51:14,000
They're not known to carry
any harmful viruses either. Lovely.

853
00:51:14,000 --> 00:51:17,120
So, could I get you to show that
to some of the audience?

854
00:51:17,120 --> 00:51:20,560
And whilst you do, I'm going to
switch over to my monitor here,

855
00:51:20,560 --> 00:51:23,880
and hopefully we've got
Professor Emma Teeling on the line.

856
00:51:23,880 --> 00:51:25,640
Good evening, Emma!

857
00:51:25,640 --> 00:51:28,520
Good evening. How are you all doing?
It's great to be here.

858
00:51:28,520 --> 00:51:31,000
Thank you. And we hear
you're the bat expert,

859
00:51:31,000 --> 00:51:35,240
so can you begin by telling me
what makes bats so remarkable?

860
00:51:36,480 --> 00:51:41,520
Well, they are the most
extraordinary of all mammals.

861
00:51:41,520 --> 00:51:46,280
Over 1,400 bat species are found
on this planet.

862
00:51:46,280 --> 00:51:50,320
That means one in five of every
living mammal is actually a bat.

863
00:51:50,320 --> 00:51:53,600
And bats are the only mammals
that can truly fly.

864
00:51:53,600 --> 00:51:57,040
Bats don't seem to age
as would be expected

865
00:51:57,040 --> 00:52:00,480
and they seem to have evolved
unique ways to resist cancer.

866
00:52:00,480 --> 00:52:02,400
And think about bats
flying at night.

867
00:52:02,400 --> 00:52:05,280
They can orient
in complete darkness.

868
00:52:05,280 --> 00:52:08,200
But what's really important
in relation to the pandemic

869
00:52:08,200 --> 00:52:12,640
is that bats seem to have evolved
a very unique immune response.

870
00:52:12,640 --> 00:52:17,360
Ancestral viruses of SARS-CoV-2
have been found in wild bats -

871
00:52:17,360 --> 00:52:20,160
never SARS-CoV-2,
but their ancestors.

872
00:52:20,160 --> 00:52:25,400
And these bats have evolved ways to
live healthily with these viruses.

873
00:52:25,400 --> 00:52:30,120
So, bats seem to have evolved a very
different innate immune response.

874
00:52:30,120 --> 00:52:32,120
Now, what is your innate
immune system?

875
00:52:32,120 --> 00:52:35,920
This is the very first barrier

876
00:52:35,920 --> 00:52:39,280
that pathogens are going to
come in touch with.

877
00:52:39,280 --> 00:52:43,680
And so your innate immune cells
are the cells that are going around

878
00:52:43,680 --> 00:52:48,040
in your body looking for pathogens,
viruses or bacteria.

879
00:52:48,040 --> 00:52:51,440
And what they do when they encounter
a virus or a bacteria

880
00:52:51,440 --> 00:52:55,760
is a normal little, calm, quiet
immune cell becomes weaponised,

881
00:52:55,760 --> 00:52:57,960
like the Incredible Hulk.

882
00:52:57,960 --> 00:53:02,200
And this weaponising allows it
to engulf and kill this pathogen.

883
00:53:02,200 --> 00:53:04,640
It makes it make all the rest
of the immune system

884
00:53:04,640 --> 00:53:06,840
also become weaponised.

885
00:53:06,840 --> 00:53:12,920
But what has to happen is we have
to be able to dial down the Hulk,

886
00:53:12,920 --> 00:53:15,240
because if you don't
your own immune response

887
00:53:15,240 --> 00:53:17,720
is going to make you
very, very sick.

888
00:53:17,720 --> 00:53:22,680
So, unfortunately, human patients
with Covid-19 that are in ICU

889
00:53:22,680 --> 00:53:26,960
have not been able to dial down
their Hulk immune response.

890
00:53:26,960 --> 00:53:30,240
And an uncontrolled Hulk
will make you very, very sick.

891
00:53:30,240 --> 00:53:34,040
But what we found was extraordinary
in the bat genomes.

892
00:53:34,040 --> 00:53:37,840
Cos when you look at their genomes,
you can see that bats seem to have

893
00:53:37,840 --> 00:53:43,760
evolved a very super Hulk response
when they encounter a pathogen,

894
00:53:43,760 --> 00:53:46,480
because you can see this expansion
of these antiviral genes

895
00:53:46,480 --> 00:53:47,800
in their genomes.

896
00:53:47,800 --> 00:53:53,360
They've also evolved an equally
extraordinary anti-Hulk response,

897
00:53:53,360 --> 00:53:57,920
which is selection and change
in the anti-Hulk genes,

898
00:53:57,920 --> 00:54:00,480
their anti-inflammatory genes.

899
00:54:00,480 --> 00:54:03,760
They've evolved the perfect
immune response -

900
00:54:03,760 --> 00:54:05,760
enough Hulk to kill the virus

901
00:54:05,760 --> 00:54:09,000
and enough anti-Hulk to be able
to live with it.

902
00:54:09,000 --> 00:54:12,280
That's fascinating, Emma.
And tell me - one last question -

903
00:54:12,280 --> 00:54:15,720
should we be worried about bats
if they've got all these viruses?

904
00:54:15,720 --> 00:54:17,120
So, we don't need to be scared.

905
00:54:17,120 --> 00:54:18,800
They're important
for our environment.

906
00:54:18,800 --> 00:54:22,000
We need to look to them
as extraordinary super mammals.

907
00:54:22,000 --> 00:54:25,040
Emma, that's absolutely fantastic
and fascinating.

908
00:54:25,040 --> 00:54:28,280
And, David, thank you also for
bringing your bat in to show us.

909
00:54:28,280 --> 00:54:30,440
APPLAUSE

910
00:54:34,200 --> 00:54:38,480
Now, bats aren't the only members
of the animal kingdom

911
00:54:38,480 --> 00:54:42,080
that could help us
in the battle against viruses.

912
00:54:42,080 --> 00:54:44,320
Now we're going to meet
another animal

913
00:54:44,320 --> 00:54:49,360
that could be important, too,
in this battle. But -

914
00:54:49,360 --> 00:54:55,560
I'm serious at this point -
no applause, please. Complete quiet.

915
00:54:55,560 --> 00:55:00,840
I'm going to welcome in,
first of all, Professor Ray Owens,

916
00:55:00,840 --> 00:55:07,920
and now Jenny, George, Barry
and some very special guests.

917
00:55:16,280 --> 00:55:18,120
There.

918
00:55:18,120 --> 00:55:24,320
So, Ray, you're the expert.
Why llamas?

919
00:55:24,320 --> 00:55:25,920
Well, these guys are really special.

920
00:55:25,920 --> 00:55:28,080
They have a special
kind of antibody.

921
00:55:28,080 --> 00:55:30,160
And the special antibodies
that the llamas make

922
00:55:30,160 --> 00:55:34,160
we can use to generate something we
call a mini-antibody, or a nanobody,

923
00:55:34,160 --> 00:55:37,840
which is really tiny but actually
can get to the site of action,

924
00:55:37,840 --> 00:55:41,320
into the virus, much more readily
than a conventional antibody.

925
00:55:41,320 --> 00:55:48,440
So, I've got a model of
a large antibody here.

926
00:55:48,440 --> 00:55:54,280
And I'm told that a nanobody is
really just that size in comparison.

927
00:55:54,280 --> 00:55:55,840
Is that right? Exactly, yeah.

928
00:55:55,840 --> 00:55:59,960
So, as you can see, it's about ten
times the size of a conventional

929
00:55:59,960 --> 00:56:03,960
whole antibody, which is the thing
we make in response to vaccine.

930
00:56:03,960 --> 00:56:06,640
So the advantage here is that
this small molecule, as I say,

931
00:56:06,640 --> 00:56:09,720
can penetrate, and we think
what's going on here is it gets into

932
00:56:09,720 --> 00:56:12,960
the spike protein and basically
stops it in its tracks.

933
00:56:12,960 --> 00:56:17,400
So we have these molecules now
that can really stop the virus

934
00:56:17,400 --> 00:56:19,840
actually binding to our human cells.

935
00:56:19,840 --> 00:56:22,280
So these are all laboratory
experiments at the moment,

936
00:56:22,280 --> 00:56:24,160
but I think there's
great prospects here

937
00:56:24,160 --> 00:56:26,320
for turning these into
potential medicines.

938
00:56:26,320 --> 00:56:30,760
So we could one day have a nanobody
discovered in a llama

939
00:56:30,760 --> 00:56:33,800
that could be a Covid treatment -
is that what you're saying?

940
00:56:33,800 --> 00:56:35,600
That's the kind of ambition,
for sure.

941
00:56:35,600 --> 00:56:38,000
And what we've done is just taken
a few cells

942
00:56:38,000 --> 00:56:41,240
from the blood of the llama. So,
when we immunise it, we vaccinate it

943
00:56:41,240 --> 00:56:43,800
as if we were giving it a shot of
the spike protein.

944
00:56:43,800 --> 00:56:47,600
We take those cells and we get the
genetic information from the cells

945
00:56:47,600 --> 00:56:49,680
which code for
these particular nanobodies,

946
00:56:49,680 --> 00:56:53,160
and then we can engineer those
into this new potential medicine.

947
00:56:53,160 --> 00:56:55,600
And the size of it also means that
it can penetrate better,

948
00:56:55,600 --> 00:56:58,440
so the idea is that it can
get into the airways.

949
00:56:58,440 --> 00:57:00,760
So you conceive this as
an aerosol spray

950
00:57:00,760 --> 00:57:02,480
that you could kind of
take up the nose

951
00:57:02,480 --> 00:57:05,080
and it would get directly
to where it needs to get to,

952
00:57:05,080 --> 00:57:07,840
where the virus is
doing its business.

953
00:57:07,840 --> 00:57:10,800
What else is going to happen
in the future with nanobodies,

954
00:57:10,800 --> 00:57:13,120
do you think? Well, I think
everything that's been done

955
00:57:13,120 --> 00:57:15,520
with whole antibodies can be done
with nanobodies,

956
00:57:15,520 --> 00:57:19,080
so I think there's great potential
here to develop new medicines.

957
00:57:19,080 --> 00:57:22,000
Particularly because, as I say,

958
00:57:22,000 --> 00:57:23,720
they can get into tissues
very readily,

959
00:57:23,720 --> 00:57:27,280
so I think there's a great prospect
and work going on now to use them

960
00:57:27,280 --> 00:57:32,160
to target, for imaging cancer cells
in tumours and things like that.

961
00:57:32,160 --> 00:57:35,840
Fantastic. So I know we all really
want to clap them,

962
00:57:35,840 --> 00:57:39,560
but we can't, so I just have to say
thank you, Ray,

963
00:57:39,560 --> 00:57:42,720
thank you, llamas,
and thank you, handlers,

964
00:57:42,720 --> 00:57:47,480
for coming on and showing us an
extra bit of science this evening.

965
00:57:47,480 --> 00:57:49,200
Off you get.

966
00:57:52,880 --> 00:57:57,040
So, we've finally come to the end
of our journey

967
00:57:57,040 --> 00:58:00,960
through the battlefield
between viruses and humans.

968
00:58:00,960 --> 00:58:05,480
These tiny things
are really incredible foes.

969
00:58:06,840 --> 00:58:09,320
They will keep on coming

970
00:58:09,320 --> 00:58:13,600
and it's really going to be
very difficult to defeat them,

971
00:58:13,600 --> 00:58:20,800
but our really astonishing science
is already helping us

972
00:58:20,800 --> 00:58:23,760
to start to fight back.

973
00:58:23,760 --> 00:58:26,440
Thank you very much.
APPLAUSE