Good evening.
Above my head is a threat...
..a bucket of gunge.
And there is a 50-50 chance that,
when the counter runs out of time, I'm going to get hit.
Should I take the risk?
Or should I protect myself?
AUDIENCE: Four, three, two, one...
APPLAUSE
Welcome.
Welcome to the 2021 Christmas lectures from the Royal institution.
I'm Professor Jonathan Van-Tam
and I'm the Deputy Chief Medical Officer of England.
But tonight, I'm actually talking to you as a
respiratory virus epidemiologist.
Now, last time, we explored how viruses like coronaviruses
can exploit human interactions to spread across the globe,
causing damage to people, to families and to societies.
And we really want to know, how can we fight back?
Now the umbrella was a bit like a vaccine.
It's a hidden defence system that you can take everywhere with you.
And perhaps vaccines against Covid-19 have been
the biggest scientific achievement of the last two years.
In the past, making a vaccine was a lengthy process -
up to 20 years, in fact.
So it's a pretty ground-breaking accomplishment, and a testament
to the quality of modern science, that we have
come so far that we can develop vaccines in under 12 months.
So what are they and how do they work?
To reveal the incredible science of vaccines, our first expert
this evening is one of the developers
of the Oxford-AstraZeneca vaccine.
Would you please welcome Professor Teresa Lambe.
I'm a vaccine scientist, and for a long time I have been
researching and making vaccines against diseases like Ebola and flu.
When SARS-CoV-2 came along, hundreds of other scientists
just like me dropped everything.
We pulled together all the knowledge we had,
our expertise, to create a vaccine...
..and it worked.
So how did we do it?
Well, our knowledge of vaccines and how they work isn't new.
It's built on centuries of scientific progress
and human knowledge.
And it stretches back around 500 years, to China.
Back then, smallpox plagued human civilisation and had done
so for thousands of years.
Here we have poor Nick.
He's got the classic symptoms of smallpox -
they're not pleasant at all.
He's got horrible pustules all over his skin that would
turn into scabs, and these were filled with highly infectious virus.
Smallpox killed about 30% of those it infected.
And it was common. It is estimated to have
killed around 300 million people in the last century alone.
But people began to notice that if you survived
smallpox infection, you would not suffer from the disease again.
You would be immune,
you would be protected against catching smallpox a second time.
Physicians at this time took this knowledge
and tried to achieve protection in a more controlled way.
To see the process they came up with, I need a volunteer.
Yes, you, come on down, in the grey top.
Hello, what's your name? Alliya. Alliya, thank you.
So, Alliya, can you just stand over here for me?
And if you just face this way, don't look at the pustules just yet,
they're a bit too gross. Thank you, Alliya.
So what I want you to do is, I want you to peel off
some of these smallpox scabs.
So you've got a forceps there and I want you to peel them off
and put them into here.
It's why I wanted a volunteer.
LAUGHTER
So scabs were chosen carefully.
They wanted scabs from people with mild, weak disease,
believing that they would be safest.
Great job.
Now, if you could grind them up.
Grind them up?! Yeah, give it a good bash.
Perfect.
So the next step is to get those ground-up scabs into somebody,
to give them the immunity to protect them from smallpox.
And one method of getting those scabs into a person
involved a nose.
That's why we've got it here.
So just wait one second.
So what I'm going to ask you to do...
..is suck some of the scabs up into this, OK?
Uh...
Just give it a bit of a suck.
Great, now follow me over here.
All the way around.
And if you can put it all the way up the nostril, that would be great.
And on the count of three, give it a big puff, OK?
Three, two, one, go!
And that's how we got smallpox scabs into people 500 years ago.
Thank you so much for your help.
APPLAUSE
So what do you think happens if you take the scabs from somebody
else's skin, grind them up and put them in someone's nose?
Do they get ill?
Well, absolutely, they do get ill.
And these people would become infected and sick with smallpox.
But if they recovered, they would develop immunity.
And, believe it or not, many people wanted this protection
back in the day.
Because about 30% of people who got smallpox
from a wild infection were dying.
But it was still a pretty risky procedure.
And when people practised this in Europe,
it killed around 2% of people who had the treatment.
So although it was far safer than catching smallpox naturally,
it's not the kind of risk that we would be willing to take today.
And it was not until the 1700s that a safer alternative emerged.
And that alternative involved a man called Edward Jenner...
..a milkmaid...
..and a cow.
LAUGHTER
APPLAUSE
Here we have Sarah, the milkmaid,
and Blossom, the cow.
They were actually their real names.
These pustules on Sarah's hands are from Blossom,
who was infected with a disease called cowpox.
It looks nasty for poor Blossom and Sarah.
Growing general knowledge at the time had demonstrated that
milkmaids like Sarah, who'd been infected with cowpox, were
immune to the much more deadly disease smallpox.
Jenner clocked onto this and started to experiment.
JVT, would you like to be Jenner? I certainly would.
What Jenner did was take a sample of the pustules from Sarah's
hands with a syringe.
I'm going to step back from this.
Come over here, Sarah.
I've got to suck up some of the pus from your hands here.
Oh, that's lovely. Oh.
Thank you very much, Sarah.
Then he injected the pus under the skin
of a healthy young boy called James.
Do we have anyone called James in the house?
Up there, at the top, in the white shirt - come on down.
So, James, it's your lucky day.
You didn't know it, but I'm going to take some of Sarah's pus
and inject it into your hand.
This shouldn't hurt.
LAUGHTER
James suffered a fever.
He was ill for nine days, but he recovered.
And two months later, Jenner exposed James to the far more deadly
disease of smallpox, but James was immune.
This was an incredible discovery.
Jenner had shown a way to gain immunity from smallpox,
but in a much safer way.
And in honour of Blossom the cow, Jenner called the technique
vaccination, because vacca is cow in Latin.
Thank you, Blossom.
APPLAUSE
OK, OK, Blossom, don't milk it.
All right, that's enough, off you go.
Thank you, Blossom, thank you, Sarah, thank you, James.
Thanks, James.
APPLAUSE
Most people wanted to become vaccinated to protect
themselves from smallpox, but some people were suspicious.
This cartoon shows some of the views at the time.
Some people believed that vaccination might actually
turn you into a cow.
Fortunately, this has not happened -
no-one has turned into a cow from vaccination.
Over time, vaccines continued to be developed to combat other
deadly diseases, too,
with huge levels of success.
So, let's see some of the diseases that vaccines have fought.
And here we have the diphtheria vaccine.
Now, before we had vaccination, in England and Wales alone,
there were 50,000 cases of diphtheria a year.
And after it...
Only one!
What have we got next?
So here...
..I've got the measles vaccine.
And again, in England and Wales before we had measles vaccines,
there were 460,000 cases each year.
And afterwards?
Just 130.
And finally, we've got a really horrible one here, of course -
smallpox. And for this one, we've really got to
talk about the whole world, because it was a scourge.
And a mid-20th century estimate...
..was that 15 million cases of smallpox occurred every
year around the world, and that caused five million deaths.
Do you know how many cases of smallpox there are each
year in the world now?
MANY: Zero.
OK, so some quite low numbers and some zeros in there.
You got it, the answer is zero.
APPLAUSE
In 1980, the horrific disease smallpox that had plagued
humanity for thousands of years was declared eradicated.
All because of global vaccination programmes.
And this was an incredible achievement of science.
Like all medicines, there can be some unwanted
side-effects from vaccines.
And for a tiny, tiny fraction of the population,
these can be significant.
But really, the probability is incredibly low and, when you weigh
the risks against the benefits, the evidence and the data are clear.
And, in fact, only one thing has ever saved more lives
in human history than vaccines...
..and that is clean water.
To understand how vaccines work, we need to understand how viruses
infect us and how our immune system works.
Like we've seen before in these lectures, let's think
of the cells in our body as a factory.
Imagine everything inside here is the inside of a cell.
But outside of the cell is SARS-CoV-2, the coronavirus.
Boo!
AUDIENCE BOOS
On the outside of the virus, you can see lots of the famous
spike protein.
The spike protein acts like a key, helping the virus
get into our cells.
Oh, no, you're in!
AUDIENCE BOOS
Once the coronavirus is inside of our cell,
it needs to copy itself, so what happens now?
Here is its genetic material.
And here is the boss' office, the cell nucleus,
where your DNA is kept, our genetic material.
Some viruses can actually break into the boss' office,
but Covid doesn't do that - it goes straight to our cell factory
machinery, the ribosome.
The ribosome is really important at making things like proteins
that our body needs.
Covid hijacks the ribosome
and inserts its genetic code to make copies of itself.
WHIRRING
Unfortunately, what this means is the virus has won.
So we've had a lot of fun with that, but there's a serious point.
We've shown how viruses can get into our cells
and copy themselves and make us sick.
So it's our immune system's job to stop this from happening.
Unlike in Jenner's time,
we now know our immune system is made of an army of things,
like antibodies from T-cells and killer T-cells that can
attack viruses and stop them in their tracks.
And, as we've seen, the immune system protects us really well
when it already remembers what the disease looked like,
either from a previous infection or a vaccination.
So let's see our immune system's memory on this board here.
It's already got some viruses on there.
This is measles, which you'll have seen either through
vaccination or have been exposed.
So you know how to recognise it and fight it off.
This one is HPV, it's a nasty virus that increases the risk
of cervical cancer, for which there is an amazing new vaccine.
But what about SARS-CoV-2?
Well, if we get infected and recover,
we will have some immunity to the virus.
Our immune system will remember it, but we want a vaccine to
train our immune system without us getting infected.
So how do we do this?
Well, let's look at some of the ways that vaccines have been developed
to fight Covid-19.
LAUGHTER
Where do you want this, love? Anywhere but on my toes, JVT.
There you go.
One method is to take the whole virus...
..but inactivate it.
So to inactivate it, we heat it up, we cool it down,
we mix it with some detergents.
A bit like putting it in a washing machine.
And that makes the virus no longer infectious.
WASHING MACHINE WHIRS
So it's a no-longer-functioning virus.
Ooh. Oh.
LAUGHTER
It may be a no-longer-functioning virus,
but it does still look like it.
Yeah.
So these whole inactivated vaccines are used to vaccinate people,
to train our immune system to recognise the virus,
to keep us safe.
So it's ready to attack the minute it sees the virus,
if it ever tries to get in.
And this is the whole inactivated vaccine method.
It's only one in a plethora of methods we have for making vaccines.
Inactivated vaccines are one of the most commonly used vaccines
to combat Covid-19.
And they're used frequently in countries like China and Brazil.
There's the virus, get it!
Well protected, immune system, you've done your job.
You've kept us safe from Covid.
But there's a bit of a mess here.
JVT? Hm.
LAUGHTER
Put your back into it.
So that's one type of vaccine,
but there are other ways to make vaccine.
Instead of helping our immune systems
to recognise the whole virus, some vaccines work by targeting
just a small piece of the virus.
For SARS-CoV-2, one of those pieces is the famous spike protein.
I helped co-design an adenoviral-vectored vaccine,
known as the Oxford-AstraZeneca vaccine,
but there are other types of vaccines just like this,
known as Janssen or J&J.
Let's see how these viral-vectored vaccines are made.
For this, I need a volunteer.
First-hand up that I saw.
Hi, what's your name? My name's Max. Max.
So instead of starting with the coronavirus,
we're going to start with something called a viral vector.
It's still a virus, but it's modified to be harmless.
So let's put this coat on and make you into a viral vector.
The viral vector is called an adenovirus.
Now, the clever part.
We swap a small part of the adenovirus' genetic code
and we give it the crucial instructions, the recipe,
if you will, to make the coronavirus' famous spike protein.
So I'm going to give you this and I'm going to take
a little bit away from you.
And that's it, we've got our vaccine.
So when we inject viral-vector vaccine,
it tries to do what viruses do - it tries to make copies of itself,
but it can't be because we've modified the adenovirus.
It can only make copies of the spike protein using the ribosome.
So if you go over to the ribosome,
and you put your spike protein in...
..what comes out?
Thousands and thousands of copies of the spike protein.
Thank you so much, Max, you've done your job.
APPLAUSE
So the cell has made thousands of copies of the spike protein.
And our immune system has now seen the spike protein
and we've made an immune memory against the spike protein.
So we're ready to attack the virus when we see it,
attacking the spike protein.
That's vaccine number two, the viral-vectored vaccine.
And that vaccine number two has already saved hundreds
and thousands of lives around the world.
So, Tess, how did it feel when you realised that vaccine had worked?
It felt like we all needed a bit of a sit down
because there'd been an awful lot of work. But, no, it felt fantastic.
The whole team had worked tirelessly for many, many months,
trying to make an impact, trying to help us get out of this pandemic.
So it was a fabulous feeling. Thank you.
So there is a third method of making a vaccine
and it's a really very revolutionary one.
It's called M, or messenger RNA vaccines.
And they go by the tradenames of Pfizer and Moderna
at the moment, so some of you will recognise them.
But actually, in terms of principles,
it's a really simple vaccine.
It is just a piece of RNA, that's all.
But, somehow, it has to get into the cell safely.
And for that...
..you have to wrap it up...
..in a package so that it can get into the cell nice and safely.
And, usually, that piece of RNA is wrapped in a package
of fats and lipids.
It sounds really easy, doesn't it?
But, actually, just to get to this stage took decades
and decades of research.
And our next expert can tell us a lot more
about messenger RNA vaccines.
So please put your hands together and welcome Dr John Tregoning.
John, tell us really how this special package works.
OK, so the RNA vaccines are trying to do exactly the same
thing as all the other vaccines, which is target the coat
of the virus and stop it getting into our cells and taking over.
But what the RNA vaccines do is take a very small component,
the spike, and just the RNA of that spike.
And the trick behind them is, they have a special modified RNA
which has been changed to make the protein factory of the cells
make more copies of that spike, better priming our immune system
to fight off the virus.
But the other thing that's helped them work so well is,
that envelope you're holding protects the RNA and
gets it into the cell better so you can make more copies.
So there's bits of technology in there that have
helped the vaccine work much better.
So was I really right when I said it's all rather simple?
No, not really.
There's been decades of research that have gone into this.
What we're seeing in the last two years is really
the end of a 20-year programme of vaccine research.
And what we're doing is building on the soldiers of giants
like Jenner, and hopefully maybe laying the foundation
for people like you in the audience, that you can build
the next generation of vaccines.
I've got to ask, if that coronavirus pandemic had come along
five years ago, or ten years ago,
would the messenger RNA vaccine technology have been ready?
So, no, I don't think so.
I think we learnt a lot from the Ebola pandemic,
or outbreak, in the 2010s.
And that taught us that the way that we develop vaccines
is not quick enough to deal with a rapidly moving viral pandemic.
And this led to change in the ways that we think about vaccines
and the way that we develop them.
All of it building on years of research but just changing
the speed at which it can be done.
Thank you, John, that's absolutely fascinating, thank you.
So tonight you've seen three very different ways
of making a Covid-19 vaccine.
And the fastest of those techniques gave us
a vaccine that was developed in just 326 days.
That is a world record and it also beats the previous
record of four years by a very considerable margin.
But the goal for the future is to go even faster.
And next time we need a new vaccine, for Covid and possibly
other diseases too, to get one in just 100 days.
But getting a vaccine recipe...
..is just the start of a much bigger challenge.
The question is, how do you get from one vaccine in a researcher's lab,
to 12.5 billion doses
projected to be produced by the end of one year?
Because that's what we're heading for at the moment, as we come
towards the end of 2021.
And the answer is, scientific expertise,
industrial expertise and teamwork.
This is a vaccine factory at work.
It requires thousands of factory workers, truck drivers,
engineers and health care workers.
And there's a huge amount of material resources
going in there, too.
Rubber stoppers, glass vials, packaging.
And there's even a problem at the other end, if you make all
these vaccines and you don't have the fridges to store them in.
Some vaccines can actually be stored in fridges,
just like the ones you have at home in your kitchens.
But others need much colder temperatures to keep
some of these vaccines stable.
And a particular one are the messenger RNA vaccines,
which are very fragile.
They require temperatures of minus 62 to 80 degrees Celsius
in order to keep that messenger RNA stable.
And for those kind of really cold temperatures,
we need lots of this stuff...
..dry ice.
And then, once the vaccines get out there to the health centres,
they still need to be administered and put into people's arms.
And for that we need a different kind of army, of health care
workers and volunteers - an absolutely huge effort.
And at the time of recording this show, a week before Christmas,
nearly 125 million vaccines have been given out across the UK.
It is the biggest vaccination programme the UK has ever run.
But vaccinating the UK is really only a small
part of the global task.
And until we are all protected across the world,
then I'm afraid to say none of us are truly safe.
APPLAUSE
The beauty of science is that all the knowledge
we have learned through Covid we can use for other diseases, too.
Viruses and diseases like Ebola, Zika, flu and even HIV.
And vaccines have even been trialled to kill cancer.
To see how this vaccine treatment could work,
let's start by looking at our genetic code.
Unfortunately, sometimes parts of our DNA can change.
This means that some proteins can change
and our cells can grow uncontrollably.
A cell has become cancerous.
Once we know what has changed in this protein
we can make a vaccine to help our immune system see the protein,
recognise it, kill the cancer cells and eradicate the cancer.
And in this way, we'll be able to make vaccines that can attack
and help protect us against cancer.
So who wants to attack a cancer cell?
You at the back, with the yellow sleeves.
Come on down.
APPLAUSE
Hi, what's your name? Oscar.
Oscar, hello, lovely to meet you.
You're going to be a killer T-cell, a destroyer of cancer.
So what I need you to do is first of all put on these goggles.
And then I need you to go over to Matt
and then put on these ear defenders, OK?
So I need everybody in the audience to put your hands
over your ears - this is going to be super loud.
OK, hands over ears.
Everybody ready?
Three, two, one...
LOUD BANG
APPLAUSE
Thank you so much, Oscar. You've killed a cancer cell,
you are a destroyer of cancer, you can take your seat.
Well done.
APPLAUSE
So we've shown you how vaccines train the immune system
to recognise threats before they even arrive.
And also how in the future they could be used to help
our immune systems to fight diseases such as cancer.
So vaccines are primarily protective measures,
but they also have the potential to cure in the future.
Tess, what are you working on these days?
SARS-CoV-2 is still keeping me up at night.
We're still looking at the immune system, looking to see
how we can combat variants of concern.
We've also found a little time to work on new vaccines,
vaccines against Ebola.
Fantastic.
Well, I wish you all the best with that work, thank you so much
for joining us all this evening to explain all about vaccinology.
Thank you so much, JVT.
APPLAUSE
So we're now in a golden age of vaccines.
Knowledge and progress that helped develop Covid-19 vaccines
in this record time have now served to kind of turbo-charge
our future ambitions in this area.
But the pandemic is not over yet.
We are now seeing the rise of the Omicron variant.
Viruses have this final trick up the sleeve, that they can mutate.
And one of the reasons why we have been
so successful in tracking the Omicron variant
is because the UK is an absolute world leader
in genetic sequencing, that's given us that ability to track the virus.
And to reveal the science of viral variants and the mysteries
of genomics, would you please welcome Professor Sharon Peacock.
APPLAUSE
So thank you and hello.
I'm a microbiologist and my job during the pandemic
has been to generate the genetic code of the SARS-CoV-2 virus
to keep tabs on how the virus is changing.
And we can see how important that is right now with the Omicron variant.
So to understand how we get variants,
we need to talk about genomes and genetic mutations.
We're not talking about mutants or comic book superheroes
with superpowers.
No, all organisms on the planet change over time
when random mutations occur in their genetic code.
So this is a model of DNA.
It's a famous double helix.
It's made up of two chains that coil around each other
and it carries the genetic code, the recipe, that makes you you,
and me me.
And that code is contained in nearly every cell in our body.
So each chain contains four different nucleotides
and we refer to them as A, C, G and T.
So imagine a string of letters
here in my spinner is a tiny
part of one of these DNA strands.
So when our cells replicate, the exact code is copied
but there is a chance that a copying error occurs, like a typo,
and another letter is introduced by mistake.
So in human cells, the chances of mutation is really very small
indeed, it one in a billion times that a cell divides.
But we're going to use this spinner today to see
if we can spot a change.
Now, take a look at the letters of the spinner.
And as I start to turn the handle, which is our simple model
of the DNA copying itself, I need you to help me.
So shout out if you see a change.
MANY: Change.
OCCASIONAL SHOUTS
ALL: Change! Yes!
Yes, there's a change.
Change! That's brilliant, thank you.
Now, for humans it's really good that genetic mutation
is very, very slow.
Mutations can make us sick - that's how cancers can arise.
But what about viruses?
Now, SARS-CoV-2 and some other viruses, such as influenza,
carry their genetic code not in DNA, but in something called RNA.
Now, RNA has a different code and structure to DNA
and we refer to it using letters A, C, G and U.
Now these viruses are genetic gamblers and up to a million
times more likely to mutate themselves in our own body.
So let's go back to our spinner.
Change. Change.
Yeah, there's a fair amount of change there, isn't there?
Yep, one more.
Change! Yes, change, thank you.
So viruses are the fastest evolving organisms on the planet.
And each time a virus code is copied,
there's a chance that a genetic error is introduced.
Now when you think about infection in a human,
the virus is copying itself millions of times, and millions
of people are being affected around the world with SARS-CoV-2.
So there's a lot of chances to mutate,
but why does it matter to us?
Well, every small change in the genetic code can have a big
effect on how the virus behaves.
One possible change is that the virus can alter in such a way
that it becomes more difficult for our immune system to recognise it.
And that's important because it's there to fight off infection.
So we are going to see how the competition between variants
and our immune system works with help from some furry friends,
which you can see on our screen, keenly waiting outside.
AUDIENCE: Aw.
They're lovely, aren't they? Look at them. Beautiful.
So our dogs are playing the parts of viral variants.
Each dog is playing the part of a different viral variant.
The cage is our cells, and variants want to get inside of our cells
to cause an infection. And if you're a dog, you get some lovely
treats if you get inside.
But playing the part of our immune system is this special
recognition system right here on this screen.
It's been trained to recognise a generic dog,
a bit like a vaccine works, but does it recognise all variant dogs?
So who will win out in the end, the variant or our immune system?
Here is our first viral variant, being played by Poppy.
Isn't she lovely?
So, Poppy's really keen to get inside the cage
and get those treats.
So let's see if the immune system recognises the variant,
let's see what happens.
ALARM BLARES
Oh, I'm really sorry,
Poppy, but look...
..you were recognised by the immune system, and out you go.
AUDIENCE VOICE DISCONTENT
Poppy failed to get past the cage defences.
Not good for the dog, but good for us because our immune system worked.
But what about dog variant number two?
This dog looks very different
from Poppy - perhaps they're faster -
but how effective will our immune system be against Luciano?
So do you think variant two will get the treats?
Yes. You do? You do think?
OK... No. No? We've got a yes and a no, so let's see, shall we?
ALARM BLARES
Oh, no.
No, our immune system has worked again and that viral variant
hasn't got into our cell. So thank you very much and bye-bye, Luciano.
OK, right, our next variant is played by Mr Fluffy.
He looks very different from other dogs, and so will Mr Fluffy
get past the recognition system
and get the treats? AUDIENCE: Aw!
What do you think - will he get through? Will he get through?
Yes or no?
MIXED RESPONSE
Oh, really, really mixed.
We'd quite like him to get the treats, but let's see what happens.
Oh, well done.
There you go, Mr Fluffy, you get the treats,
and there's quite a lot there for you to eat.
So the variant is different enough to avoid
recognition of our immune system.
He got past our immune system and we will be infected.
It's good for Fluffy, particularly as he's got so much chicken,
but really bad for us because we've become infected.
So thank you very much to Mr Fluffy.
And I'm really sorry, Mr Fluffy, but you're going to have to go.
DOG BARKS
That dog didn't get the chicken.
MULTIPLE BARKS
So, you know, this is a lot of fun but there's a really serious point
to Mr Fluffy's success, because variants really matter to us.
Because they can get past our immune system and variants
are something we have to monitor very closely with Covid-19.
If a virus variant becomes more transmissible,
it could spread more quickly and cause more cases.
Variants could also make us more unwell if we're infected.
Unlike we saw just now, variants may start to evade our immune
system defences, and these are what we call variants of concern.
Dodging our immune system is the worry with Omicron.
So, JVT, can you give us a quick update on Omicron?
Right now, at the time of recording, a week before Christmas,
there's a lot we don't know about Omicron.
But what we can say is that it is already growing very, very fast
in the UK, and it will have grown some more
by the time this programme goes out on the air.
And that's despite many of us already having been vaccinated.
And it seems like this variant is partially dodging the vaccine.
And that's why it's making it really important for adults
to have a booster dose, and early data is now beginning to show
that this is going to reduce the risk of being infected.
Thank you very much, JVT.
So, let's take a look at what is changing with this virus.
Let's zoom in on the spike protein, which decorates the outside
of the coronavirus, to see how much it has changed over time.
So we're going to look at this image here.
So, these show the spike proteins of three different variants.
On the left is the original virus that first emerged.
The middle is the Delta variant that's still circulating among us
and across much of the world at the moment.
But this is the spike protein for Omicron.
Now, you can see how different they are,
and the red and the blue indicates where the spike protein has changed.
Now, Omicron has around 50 different mutations in the entire genome
compared with the early virus
and around 30 concentrated in that spike gene.
Now, that's a lot of change.
And it means that the spike looks different to our immune system.
And it's so different that this is why we're being asked
to get a booster, to increase our immunity.
So how do we keep track of variants?
Well, everything really hinges on having the complete genetic code
of the virus or its genome, and this comes down to huge advances
in genetic sequencing technology over the last 30 years.
So, let's take a look at how far we've come.
Now, 20 years ago,
the Human Genome Project was finished
and we decoded the DNA of a human.
So, see the result here -
118 hardback books containing over three billion base pair letters.
Now, the cost was £2 billion and it took 13 years to complete.
Ten years ago, the cost of sequencing a human genome
had dropped to £38,000.
And now, as technology has got more automated,
the human genome can be sequenced for under £400.
And now we get the chance to see just how simple it is to do.
APPLAUSE
Here we have Kim Judge from the Wellcome Sanger Institute.
And she'll be showing us the latest sequencing technology.
So, Kim, can you tell us what you're going to show us today?
Sure. So, here we have a hand-held sequencing device.
And we can use this to sequence the genome of SARS-CoV-2.
Oh, so that's safe, is it? Completely safe, yes.
We've prepared it in a lab earlier,
there's no longer a virus present,
it's just genetic material. OK.
So can you show us what you're going to be doing
to set up the machine to sequence? Sure.
So I've already input some details about what we're going to be doing
onto the touch screen here. I'm going to open this up.
And we have a small hole that we can pipette the DNA into.
So this is the pipette. I'm just going to give it a little mix.
Just move it up and down a bit like that.
And then, with a very steady hand,
just squirt it on here.
So...once we've done that, we can close it all back up again.
It's just going to take a couple of moments to sort of drink
the liquid in, and then we can press this button here for start.
That's amazing, isn't it, that you can sequence in this theatre?
That simply is quite extraordinary.
But I know it's going to take a few minutes to get going. That's right.
And you've brought another machine that's just slightly further ahead,
so we can actually see some of the sequence data being read out.
That's correct. So, we've got one here that's been running
for just a few minutes already.
So what you can see here is, actually,
those green boxes represent the genetic code,
including the mutations that might suggest that this is a variant.
Indeed. Yeah.
I mean, the fact that this is such a small piece of kit means
that you could take it anywhere.
And I wonder if you can tell us the most exciting place
it's been used to sequence something.
I mean, there's quite a few places it's been, but I think
the coolest place, probably, is the International Space Station.
That is pretty cool, actually. OK, well, thank you for coming, Kim.
Thank you very much. Thank you. APPLAUSE
So, something that is really unprecedented during the pandemic
is we have generated more than 5.5 million SARS-CoV-2 genomes
around the world.
We monitor tiny changes in the virus's genetic code
in close to real time as possible.
Now, pathogen genomics has actually never been able to do this
on this scale or speed before.
So we can see the advantages of this for Omicron.
Genomic scientists and vaccine scientists
are working very closely together as a team.
And the genetic code of Omicron, identified last month
on 23 November, was fed through to vaccine makers.
And they've been working on new vaccines specific to Omicron.
They predict they could be ready to vaccinate us in just 95 days.
And this is staggeringly fast.
So, we can merge all of our genomic information
to build up a vast virus family tree,
which you can see on this screen, for the United Kingdom.
Now, each colour that you see represents a viral variant,
and you can see over the course of the two years of the pandemic
how that's changed over time.
Now, in the first part of the pandemic,
you can see there's a great deal of different variants,
none of which are really outcompeting the other.
So, through random mutation and natural selection,
perhaps one will win the jackpot because it's more competitive
than the other. This is like a fitness race.
And this is what happened when Alpha emerged.
So, on the green here, you can see Alpha becoming very dominant
in the population.
Here, you can see that Delta then emerged
and actually outcompeted Alpha.
And right at the very far part of the chart here,
you can see - in red - Omicron.
Now, that looks very small at the moment,
but actually this chart only goes up to the beginning of December.
And what we're predicting is that, by Christmas or into the new year,
that red will go right the way up and become dominant,
as the dominant variant.
So we need to expect much more from this variant,
and what we need to celebrate, in fact,
is that we've got eyes on the virus all of the time
in a way that we really never have achieved before.
And that's a very good thing for us.
If these viruses keep hitting the jackpot,
then will we continue to see these further changes in the future?
Well, I'm sure that SARS-CoV-2 has got a few more tricks up its sleeve.
I think we're going to see more variants actually emerging.
I think a really important question is whether it will mutate itself
out of fitness, because only so many changes in the genetic code
can really be managed together
before the virus starts to lose its fitness.
So, in the end, it's possible that the virus will become
like the common cold, nothing more serious than that,
but we haven't really reached that point yet.
So we just have to stay vigilant until we get there,
because we don't know the future?
Yeah. Absolutely vigilant. And we've got the technology to do that now.
How does it feel to be part of that big effort?
Well, it's really amazing to have been in the right place
at the right time. And just a few years ago,
we wouldn't have been able to provide this vital information
in the pandemic response, and so that's incredible.
I would say, though, that we've achieved this through the work
of a great many people, so I pay tribute to all of those people
that have helped us. So, pathogen genomics is really here to stay.
We can use it to fight future pandemics
and we can also use it for other threats,
such as antibiotic resistance.
How far, where could we actually go with genetic sequencing in the end?
What we could do is defied by my own imagination,
because we are currently sequencing all of life on Earth.
We can sequence our own genome,
we can sequence the microorganisms in and around us,
we can sequence in hospitals, clinics, the jungle, in space.
And I find it very difficult to imagine what that will lead to.
But, actually, I think it will provide new information
to help humans stay healthier and actually help preserve our planet.
Sharon, thank you so much for showing us
inside the world of genomics this evening.
You've been fantastic. Thank you very much, JVT.
So you've seen that the secrets to success
might lie in the genetic code. And it raises a question.
Through that, can we be better prepared for the future
and could part of that better preparation come from finding
where these viruses actually come from in the first place?
So if we trace back to the very earliest variants
of this coronavirus pandemic, we can actually start to gather some clues
about where it might have come from.
And there are some possible hints that lead back
to a most remarkable creature - the bat.
And I'd like to welcome David King.
APPLAUSE
And if you look carefully on the screen, David has a bat with him.
David, what species of bat do we have here?
This is a pipistrelle, which is the smallest of 17 British species.
Despite its small size - it only weighs 5g,
which is the same weight as a 20p piece -
it can live 15 years
and each night it can consume 3,000 mosquito-sized insects.
Can you tilt it towards the camera?
So, David, is it safe to have a bat in here, in the lecture theatre?
It's trying to escape all the time, obviously,
because it's not a natural environment,
but it is safe because it's a captive bat that has been rescued
because it was injured or abandoned as a baby,
so it's not a good flyer.
They're not known to carry any harmful viruses either. Lovely.
So, could I get you to show that to some of the audience?
And whilst you do, I'm going to switch over to my monitor here,
and hopefully we've got Professor Emma Teeling on the line.
Good evening, Emma!
Good evening. How are you all doing? It's great to be here.
Thank you. And we hear you're the bat expert,
so can you begin by telling me what makes bats so remarkable?
Well, they are the most extraordinary of all mammals.
Over 1,400 bat species are found on this planet.
That means one in five of every living mammal is actually a bat.
And bats are the only mammals that can truly fly.
Bats don't seem to age as would be expected
and they seem to have evolved unique ways to resist cancer.
And think about bats flying at night.
They can orient in complete darkness.
But what's really important in relation to the pandemic
is that bats seem to have evolved a very unique immune response.
Ancestral viruses of SARS-CoV-2 have been found in wild bats -
never SARS-CoV-2, but their ancestors.
And these bats have evolved ways to live healthily with these viruses.
So, bats seem to have evolved a very different innate immune response.
Now, what is your innate immune system?
This is the very first barrier
that pathogens are going to come in touch with.
And so your innate immune cells are the cells that are going around
in your body looking for pathogens, viruses or bacteria.
And what they do when they encounter a virus or a bacteria
is a normal little, calm, quiet immune cell becomes weaponised,
like the Incredible Hulk.
And this weaponising allows it to engulf and kill this pathogen.
It makes it make all the rest of the immune system
also become weaponised.
But what has to happen is we have to be able to dial down the Hulk,
because if you don't your own immune response
is going to make you very, very sick.
So, unfortunately, human patients with Covid-19 that are in ICU
have not been able to dial down their Hulk immune response.
And an uncontrolled Hulk will make you very, very sick.
But what we found was extraordinary in the bat genomes.
Cos when you look at their genomes, you can see that bats seem to have
evolved a very super Hulk response when they encounter a pathogen,
because you can see this expansion of these antiviral genes
in their genomes.
They've also evolved an equally extraordinary anti-Hulk response,
which is selection and change in the anti-Hulk genes,
their anti-inflammatory genes.
They've evolved the perfect immune response -
enough Hulk to kill the virus
and enough anti-Hulk to be able to live with it.
That's fascinating, Emma. And tell me - one last question -
should we be worried about bats if they've got all these viruses?
So, we don't need to be scared.
They're important for our environment.
We need to look to them as extraordinary super mammals.
Emma, that's absolutely fantastic and fascinating.
And, David, thank you also for bringing your bat in to show us.
APPLAUSE
Now, bats aren't the only members of the animal kingdom
that could help us in the battle against viruses.
Now we're going to meet another animal
that could be important, too, in this battle. But -
I'm serious at this point - no applause, please. Complete quiet.
I'm going to welcome in, first of all, Professor Ray Owens,
and now Jenny, George, Barry and some very special guests.
There.
So, Ray, you're the expert. Why llamas?
Well, these guys are really special.
They have a special kind of antibody.
And the special antibodies that the llamas make
we can use to generate something we call a mini-antibody, or a nanobody,
which is really tiny but actually can get to the site of action,
into the virus, much more readily than a conventional antibody.
So, I've got a model of a large antibody here.
And I'm told that a nanobody is really just that size in comparison.
Is that right? Exactly, yeah.
So, as you can see, it's about ten times the size of a conventional
whole antibody, which is the thing we make in response to vaccine.
So the advantage here is that this small molecule, as I say,
can penetrate, and we think what's going on here is it gets into
the spike protein and basically stops it in its tracks.
So we have these molecules now that can really stop the virus
actually binding to our human cells.
So these are all laboratory experiments at the moment,
but I think there's great prospects here
for turning these into potential medicines.
So we could one day have a nanobody discovered in a llama
that could be a Covid treatment - is that what you're saying?
That's the kind of ambition, for sure.
And what we've done is just taken a few cells
from the blood of the llama. So, when we immunise it, we vaccinate it
as if we were giving it a shot of the spike protein.
We take those cells and we get the genetic information from the cells
which code for these particular nanobodies,
and then we can engineer those into this new potential medicine.
And the size of it also means that it can penetrate better,
so the idea is that it can get into the airways.
So you conceive this as an aerosol spray
that you could kind of take up the nose
and it would get directly to where it needs to get to,
where the virus is doing its business.
What else is going to happen in the future with nanobodies,
do you think? Well, I think everything that's been done
with whole antibodies can be done with nanobodies,
so I think there's great potential here to develop new medicines.
Particularly because, as I say,
they can get into tissues very readily,
so I think there's a great prospect and work going on now to use them
to target, for imaging cancer cells in tumours and things like that.
Fantastic. So I know we all really want to clap them,
but we can't, so I just have to say thank you, Ray,
thank you, llamas, and thank you, handlers,
for coming on and showing us an extra bit of science this evening.
Off you get.
So, we've finally come to the end of our journey
through the battlefield between viruses and humans.
These tiny things are really incredible foes.
They will keep on coming
and it's really going to be very difficult to defeat them,
but our really astonishing science is already helping us
to start to fight back.
Thank you very much. APPLAUSE