So what I'm going
to do today is I'm
going to take you on a
whistlestop tour of immunology.
I will hold your hand
all the way through it,
so it shouldn't
terrify you too much.
With a little smattering of
microbiology and parasitology
and show that how we
learn about these subjects
is helping us to find new
ways to heal ourselves.
And before I get started,
I'd like you all to help me
with a little experiment.
So could you turn to
somebody on your right side,
your left side, behind
you, shake their hand,
and say hello.
And I'll come and do it too.
Can I say hello?
Hello, nice to meet you.
Hello, nice to meet you.
I'll say hello to you.
Nice to meet you.
And I'll say hello to you.
Nice to meet you.
[INTERPOSING VOICES]
OK.
So I'll explain why later
on, but don't worry,
I won't forget.
OK, so immunology has got a
little bit of a reputation.
So I'm going to try and
explain to you now what
I mean by immunology.
And this is a very, very typical
cartoon of an immune response.
And typically, this
is very much the way
that immunology is described.
It's thought of as the way that
our bodies evolved this defence
system to be able to deal with
a whole range of infectious
organisms.
So when you see
descriptions of immunology,
you hear about weapons
and armies and warriors,
and it's very, very
war-like and aggressive.
And indeed, we have
evolved to deal
with a whole range of different
infectious threats, all the way
from the very, very
small viruses, which
can be 20 to 400 nanometers
big, through to bacteria,
fungi, yeast, through
the parasites.
And the biggest ones are the
parasitic worms like tapeworm.
And that could be
about nine metres big.
So that's a range of scale of
around 10 to the power of 9.
Now that might seem
like a big number,
but let's try and put it
in some context for you.
So if I was the size
of an immune cell,
a bacteria would be about
the size of a rugby ball.
And that very
largest virus would
be about the size of a
double A battery, the kind
that you put in an
Xbox controller.
And the very
smallest virus would
be about the size of a
paracetamol, a tablet.
I'm not going there
with a tapeworm.
I don't think it would
fit in this room.
So you get that kind
of sense of scale.
And somehow, your
immune system can
cope with this huge challenge.
And the way it does, it
recognises unique structures,
unique features to all of
these different pathogens.
And these are called antigens.
So it recognises these unique
features called antigens.
But of course, I told
you that immunology's
got a reputation
for being complex,
and it really isn't as simple
as that because not only do
we have to deal with
all these threats,
we are also colonised
by a huge array of yeast
viruses, bacteria, and
even some parasites.
And these, of course,
make up our microbiota,
or a microbiome, which
refers to the genetic content
of these things that
live inside us and on us.
And this is actually a
cross-section of the guts.
And what you see here
is the epithelial cells
that line the gut.
They've got little blue nuclei.
And some of these epithelial
cells are making mucus,
and that's what all
the green stuff is.
It's aptly coloured.
And then you have
this mucus layer here.
And all these red
speckles are bacteria
living in the large intestine.
And the number of
bacteria, which
is what we know most about,
is absolutely staggering.
Each one of you has
38 trillion bacteria
living on you and in you.
Now that seems big.
But how about we compare
that to the whole planet?
So if we look at the
population of humans
on the planet drawn to scale--
and that's one of your
bacterial populations.
So your bacteria are dwarfing
everybody on the human planet.
Human planet?
And that's roughly how many
bacteria live on everybody
on the planet, which is
2.9 times 10 to the 23,
which is absolutely staggering.
And they're really,
really diverse and varied.
And as an illustration,
this is actually
an agar sculpture
that's been made
by an artist called Mel Fisher.
And what she does is-- agar is
a substance that we can grow
bacteria on, so she casts
these agar models of her face,
and then she takes little
bits of her own skin,
she kind of scrapes her
skin, and then seats it
onto the model to create this
image of some of the bacteria
on her skin.
And if she changes
the agar mix or uses
a different part
of her skin, she
gets a completely
different model.
And there's actually some
fungi growing there, as well.
So that gives you a very
visual representation
of how varied
these bacteria are.
And even if you think
about your skin,
you've got three very
different landscapes.
So the back of your
arms are an example
of a very dry, arid landscape.
You have the oily zones,
like the t-zone on your face,
your nose and your chin.
And so different
bacteria will live there.
And then you've got all
your folds and creases.
You know your folds
and increases.
And you've got very,
very different bacteria
living there.
And even between your
folds and creases,
there could be quite
a lot of variation,
so your toes will not
have the same thing,
say, as under your armpit.
And so that gives you a really
good idea of the variation.
And they're very
important to our health.
They are helping our immune
system function properly.
They are educating
our immune system.
They're helping us
digest our food.
They're making important
vitamins we couldn't make.
So our immune system has to
be able to cope with this
and not attack them.
And again, it will do this
by recognising antigens.
Now there's another
form of antigen
that we take into our
body in a huge amount.
Does anybody know what it is?
Anybody think?
Somebody whispering it?
Food, that's right.
So that is one of
the biggest antigens
that we take into
our body every day.
We are putting kilos of
foreign antigens into our body.
Yet, by and large, our
immune system, again,
copes well with this.
And it's not just the
foods that we eat.
I mean, some of them could
be particularly challenging,
but it's also the
things that belong
to us that your
immune system has
to be able to tell
the difference with.
So it needs to look all the
parts of you, your tissues
and cells, and understand what's
you so it doesn't hurt them.
So when you take this
into consideration,
you really get quite a different
image of the immune response
because actually what it's doing
is acting as a peacekeeper.
It's mostly ignoring things
and stopping immune responses
from happening.
And even when it does react,
you need the immune response
to be really tightly
controlled, otherwise you're
going to have
unintended consequences,
and nobody wants that
to happen in their body.
So this means that we
have a whole series
of checks and balances that
operate in the immune system.
And the more we know about
how these things work,
the more we can exploit
the immune system.
Now one of the most important
cells in the immune system
is this.
Is a T lymphocyte.
It's a white blood cell.
And these are the most
important cell type
at dealing with infections.
They can destroy a whole
range of different infections
and they can also be
really tolerant to things.
But there was a really
big puzzle in immunology
because we knew T cells did
all sorts of amazing things,
but we didn't know how they
got the information to do that.
How does a T cell know?
It's got no way of
recognising antigens,
so there must be another part
of the immune response that lets
the T cell do that.
And that was really the
life's work of Ralph Steinman.
So in 1973, he was
attributed with discovering
the missing piece
that instructed the T
cell with what to do.
And that's called
the dendritic cell.
So we have an image here
of a dendritic cell.
And you can see that it's
got these long processes
or dendrites.
And what they do is they take
information from pathogens
or your commensal bacteria,
they process it just right,
and they give it
back to the T cell.
And Ralph Steinman was
working on them in the states,
but actually, around
the same time,
there was a British
scientist called
Brigitte Balfour who
was working on a cell
type she coined veiled cells.
And it turned out that they were
actually the same cell type,
but they were of a different
developmental stage.
So perhaps he wasn't
alone in his discovery.
And what they do is they
basically take those antigens
and they make them into these
beautiful, bite-sized fragments
that the T cell can see.
And to do this, they use
something called Major
Histocompatibility Class, MHC.
And basically, what
you have is you
will have MHC presenting
the antigen to the T cell.
Now other cells can express MHC.
And I already told you that we
don't want your immune response
to be inappropriately activated.
So that means the dendritic
cell has an extra switch
to help the T cells do that.
It's called co-stimulation,
and it's only
when that extra interaction's
present that the T
cells get switched on.
That's just an example
of how tightly controlled
the immune response actually is.
And so now that we know how
important dendritic cells are,
can we start to use
this information
to help us find treatments.
And this is an area that
we're looking at in my lab.
We're very interested
in understanding
how you go from a normal
state to an inflamed state,
and an inflamed state
that is unregulated.
So these are images of the gut.
And are there
particular pathways
that will predict whether
that's going to happen?
And one of the models
on this is a sort
of image showing endoscopes.
So you saw the
cells, and now you
see the endoscope images of
normal gut versus inflamed gut.
So one of the models
that we use is
whipworm, which is a
parasitic worm that
lives in your large intestine.
And it has a really
well-characterised
immune response
because you're either
resistant to the
infection, in which case
you kick the worms out.
You have a really
strong T cell response,
you kick the worms out, and
your inflammation resolves.
Or you're susceptible
to the infection.
You keep the worms, and
what you end up with
is an inflamed gut
that looks an awful lot
like inflammatory bowel disease.
So this gives us a
really good model
to start to ask questions about
inflammatory bowel disease
because we know the
T cell responses,
but we don't know
what's happening
with the initiation, that
dendritic cell that's
critical for the switch.
So that's what we
started to look at.
And to our surprise,
we saw there
was a very, very
different dendritic cell
response in resistance
versus susceptibility.
So what we have here is a
picture showing you the gut.
The epithelial
cells are in green,
and all those red things
are dendritic cells.
There was a massive recruitment
of dendritic cells very,
very quickly in resistance.
That didn't happen
in susceptibility.
So the T cells weren't
getting the right signals
to know what to do in time.
Then we could ask which pathways
were driving that very, very
different response.
And what's been really
exciting for us is
we've identified proteins
that we can pick up in poo
and we can pick up in serum.
And what that does is it
enables us to go and think
about screening patients
to monitor their disease
and track when they're
getting a flare up
and try to do
interventions even earlier.
So this is an
example of how we're
going from very
basic research ideas
to trying to take
something that we'll be
able to translate into benefit.
And Ralph Steinman
also really wanted
to use his discovery of
dendritic cells to try
and have patient benefits.
And of course, he was awarded
the Nobel Prize for Medicine
in 2011 for his whole body
of work on dendritic cells.
And his particular interest was
in the world of cancer therapy.
Now cancers and tumours
are really problematic
for your immune response,
and that's because they look
a little bit like us.
And I already told you that
are your immune response
is fairly well-programmed
to ignore you.
And they also actively
suppress the immune response.
So that makes it really, really
hard for your T cells to do
what you want them to
do, i.e. kill the tumour.
But what Steinman
wondered was could
you change that by
programming dendritic cells.
So what he proposed you could do
is you could get your patient,
you could take their blood,
and grow up dendritic cells
from their blood.
You could take the patient's
tumour and you could extract
the proteins from that and
feed it to the dendritic cells.
Then you could put the dendritic
cells back into the patient
and they would educate the
T cells and that would help
the tumour be destroyed or
any remaining cancerous cells.
Now the good news is
this was absolutely safe.
The bad news is it
didn't really work.
However, it's been refined.
And the reason that
it's been refined
is because we now know that
there's lots of other factors
we need to take
into consideration.
There are lots of different
types of dendritic cells.
We now realise that only certain
types of dendritic cells are
good at killing tumours,
so we need to target those.
We know more about how
dendritic cells get activated.
We know more about
the sort of antigens
that are going to be better
at activating dendritic cells.
And we also know that it's
really important to look
at the patient's status.
So when you take all these
things into consideration,
this is looking a very much
more promising treatment.
And it's personalised
to each patient
because it's their
cells and their tumour.
So I think this is a
really exciting future
in immunotherapy.
And then if we
move on, we've got
the initiation of the response,
but what happens once the T
cells are already activated?
Now I told you that there's
a problem with tumours.
Tumours are inherently good
at switching off T cells.
And the way they do
this is basically
exploiting a normal mechanism.
So when you've got your T
cells all activated and killing
a pathogen or
pathogen-infected cells,
you want them to stop when
you've got rid of the pathogen.
You don't want them to
keep doing lots of damage
to your body.
So that means we
have off switches.
We have ways that can
switch your T cells off.
Now the tumour is exploiting
this and doing this naturally.
So it's switching your
T cell off artificially
a bit too quickly.
But now we know what
these off switches
are, or checkpoints,
so the ways of putting
the brakes on immune responses.
And this was awarded
the Nobel Prize in 2018,
and it was awarded to James
Allison and Tasuko Honjo.
And they were working
on these checkpoints.
They were working on two
different checkpoints,
two different ways that
T cells get switched off.
And what they
proposed was that you
could use antibodies that would
block those checkpoints so
that the T cells would
stay switched on.
And that's what they did.
This is what it looks like.
So when you use the antibody,
the tumour now is enabling T
cell activation to take place,
and the T cells will then kill
the tumour.
Now this is also
in clinical trials.
It's also being
used in treatment.
Because they're two
different targets,
they can be used together.
And it does work.
It does seem to really work.
Not in all cancers, not for
all patients, but again,
it's looking really promising.
And because it's a different
therapy to the dendritic cell
therapy, you could perhaps see
them being used in conjunction
also with conventional
chemotherapies, which
is all quite exciting.
But like anything with
immunology, there's a catch.
And this is the catch.
Patients who had antibiotics
didn't respond well
to checkpoint inhibitor therapy.
Patients who had
high-fibre diets
responded really well to
checkpoint inhibitor therapy,
all of which suggests that
something about the microbiome
is important when
it comes to drugs.
And we already kind of knew
that because we've seen it even
in nature.
So this is a cotton rat.
Sorry, at desert rat.
It's not a cotton rat.
And as the name implies,
it lives in the desert.
And food's obviously
not very plentiful.
But one thing that does grow in
abundance is the creosote bush.
Now creosote bushes
are poisonous.
They are deeply toxic to most
things, but not the desert rat.
They're very, very
comfortable eating them.
Why is that?
It turned out it was
because of the microbiome.
So if you gave a
desert rat antibiotics,
they couldn't eat the
creosote bush anymore.
It would kill them.
If you transferred the
bacteria from a desert rat
into a normal rat,
the normal rat
could suddenly eat creosote
bush without being killed.
So that shows you the power
of the microbiome in dealing
with metabolising poisons.
And we already knew
that it could affect us.
This is foxglove.
And from foxglove,
we isolate digoxin.
This is a drug that's
used to make heart beats
and go more strongly and slowly.
But in around one in 10 people,
it doesn't work very well.
Even simple drugs
like paracetamol
don't work in some
people as well as others.
It's all down to changes
in the microbiome, which
are breaking down
the active substances
or preventing the act of
substances from being released.
So that suggests that
perhaps what we'll ultimately
need to do is we'll need to
screen your microbiome when
we do any kind of
prescriptions so that we
can try and optimise and
match the treatment for you.
But can we change the microbiome
to make the treatment optimal
for you?
And that's the big question.
Now the obvious route
that a lot of people
will go to when we want
to change the microbiome
are these.
Probiotics.
Everybody's heard of probiotics.
You can buy all sorts
of probiotic products
on the shelf.
And these are sort of
friendly, helpful bacteria.
But the evidence for probiotics
is pretty mixed, in truth.
Probiotics have been shown to
have some beneficial effects
on transient gut
inflammation, things
like antibiotic-induced
inflammation.
They may also help in
some gut conditions
like necrotizing enterocolitis
or inflammatory bowel disease.
But the biggest
problem with probiotics
is that they don't
necessarily get
to where you want to get to.
So when I showed you that
image of the cross-section
of the gut, you saw there was
a lot of bacteria that were
sitting in the mucus layer.
And actually, that
population of bacteria
is really resistant
to colonisation
by probiotic species.
So the probiotics aren't
able to get to everywhere
that you want them to get to,
not by our conventional roots.
So they may not always
be the most effective.
But they still have
some interesting uses.
And we've actually
been looking at them
in the context of this,
which is wound healing.
So around one in 20 of us,
particularly as we get older,
are going to develop
wounds that fail to heal.
And one of the biggest
complications of those wounds
is infection.
And that can be a real
problem, and it can even
cause amputation.
So finding ways to
better treat these wounds
is really, really important.
And one of the things that we've
been researching in the lab
is could we use probiotics?
And what we do is we actually
smash up the probiotics.
The probiotics aren't live.
And we've shown that they
can inhibit pathogens
from binding to the skin,
they can kill some pathogens,
and they may even help
the skin layer regrow.
And I guess that it's a
little bit easier when you're
talking about skin
because you haven't
got the issues of trying to get
it to the right area in the gut
because you can just
apply it topically.
So there could be some really
interesting applications that
could come out of probiotics,
and not just in the skin field.
So probiotics may
not be the answer
if we want to change
our microbiome.
Anybody know what this is?
Are you being really quiet
if you do know what it is?
OK.
So this is an enema kit.
And enemas have
become pretty trendy.
There's quite a few
very famous celebrities
who really advocate
the use of enemas.
So essentially, what
it is-- and this
is one of the oldest
forms of medicine.
You go back in history and
people used to do enemas
all the time--
you basically-- there's
other enema kits
that look a bit like hot
water bottles, as well.
You get a long tube and
you kind of, basically,
syphon quite a lot of liquid
into your back passage.
Sometimes it's coffee.
I don't know why.
And basically what
that's supposed to do
is for us to kind of flush
out and cleanse your gut.
But, of course,
what it's doing is
removing maybe any residual
stool that you might have,
but it's also almost certainly
damaging your mucous layer
or so many of your
important bacteria live.
So it's massively
depleting your microbiome.
You can then go
one stage further.
A few of you, you
know where I'm going.
So say there's this
remarkable person
who's just lovely and
thin and wonderful
and you think, I
want a bit of that.
So you just asked
them for a poo sample.
You pop it in there.
You pop it in the
blender and whizz it up.
And you essentially
make a smoothie.
And then you can reapply
it, reinsert it back
into your body, often rectally.
Sometimes it can be
turned into tablets.
And sometimes they're
used in the-- the--
yeah, I'm not going
there anymore.
And this is called faecal
microbial transplant.
And weirdly, there is also lots
of self-help videos telling you
how to do this.
There are parties telling
you how to do this.
And it's probably
the number one reason
that you should never, ever,
ever buy a second-hand blender.
So why would you want to
do such a drastic thing?
Well, it comes down to this.
This is Clostridium difficile.
So this is a bacteria
that can be resident
in our gut in small
numbers, but unfortunately
for some individuals,
often older individuals who
have been in hospital,
this can really
outnumber all the other
bacteria in their gut.
And when this happens, it
causes a really unpleasant gut
inflammation, really severe
diarrhoea, and guess what?
It's really hard to
treat with antibiotics.
They don't respond
well to antibiotics.
So this is a really,
really big issue.
But if you-- this is what
the poo smoothie looks like.
If you administer
one of these, you
can restore the gut
completely, really quickly.
It's remarkable.
But, of course, this is done
under clinical supervision.
The donors have been
screened to make sure
that they're not going
to give you an infection,
and there's been a lot of
thought that's gone in.
And then you will
be tracked, as well.
And changes in gut
microbial communities
have been associated with a
whole host of other conditions,
like, for example,
multiple sclerosis.
So are they causing some of
the inflammation that we see?
We don't necessarily
know, but that's not
stopping some clinicians
investigating this further
as possible treatments.
But again, always under
clinical supervision.
So this is a way that you can
change your gut microbiota,
but probably not
something that you're all
going to want to try at home.
And one of the biggest problems
with this idea is, as I say,
it's the gut architecture.
Now I showed you those images
of Mel's agar sculptures.
You could see how varied the
microbiota was in your skin.
It's also true if you've got--
you have an enormously varied
microbiota in your gut
with changes in the numbers
and types, all the
way from your stomach
all the way through to
your large intestine.
And where they are
is really important,
as well, because
these bacteria that
are found here in
this mucus layer
that I told you
about before, they're
very, very close to our
cells and our immune cells.
So they're probably the microbes
that are the most important
for our health, yet a lot
of the analysis that's
telling us about
microbial differences
is based on stool samples.
Is that telling us what's
happening in the mucus?
And the answer is no.
So we and others have shown
that the mucus resident bacteria
is quite different
from the bacteria
that you find in the stools.
And if you look at a disease
like inflammatory bowel
disease, you can
detect differences
in the mucus bacteria
long before you
can detect any differences
in the stool bacteria.
So the stool bacteria
really might not
be giving us an accurate
reflection of what's
happening in our body.
And I think, as well,
until we know more
about those bacteria that
are closest to our cells,
I would once again
urge you not to make
yourself a poo smoothie.
And there's another issue.
Don't worry, you're not supposed
to be able to read this.
This is data from my lab.
This is actual microbiome data.
This is one of four pages.
And this is-- we're
talking really big data.
This is what it comes like.
I'm a biologist.
And what biologists do is
we go, that's a top change.
That's going to be important.
Yep, that's the top change.
That's going to be important.
We rank.
Seems logical.
That's not how the
microbiota works.
It works as communities.
It's a whole community doing
a job, not one bacteria.
So a single change
in bacteria might
have no impact functionally.
So we need to be thinking
differently about how
we look at the microbiota.
We need to be thinking
about how they're organised.
So this is an example
of some approaches
we've been trying
in the lab where
we're looking at communities
of the microbiome now.
So we're instead of
looking at them singly,
we started grouping them
as to how related they are.
So this is a phylogenetic tree.
And so all the bacteria here
are very, very closely related
together.
These are sort of like
your great, great, great
grandfathers, and
these guys over here
are not related to you at all.
And what we've done here is
we've coloured this according
to whether they live
in the mucus and stool,
just as a nice illustration.
So all the pink bits
are the mucous bacteria,
and all the brown bits, aptly
enough, are the stool bacteria,
just to again
illustrate that they are
quite different communities.
So this is going to give us
some different ideas about how
bacteria are changing and
the changes that matter.
And what a lot of
people, our lab included,
are also trying to do is
look at the functional
outputs of the bacteria,
the products that they make
and how that's going to
impact on the function
of our immune system
and our health.
So I think there's
still a lot to learn.
And the other issue, I
guess, with the microbiome
is that predominantly,
we're still just studying
the bacteria, yet there are
a host of viruses and fungi
and yeasts, a few
parasites in there, too,
that are also going to
be having an impact.
So there's an awful lot
more that we need to do.
But I guess you still
want to know how
you can change your microbiome.
So studies have looked at
healthy octogenarians, people
who just-- they're fantastically
healthy as they get old.
And if you compare
them with people
who are quite frail
as they get old,
one of the biggest differences
is in their microbiome.
And these very healthy people
have very varied communities
of bacteria in their guts.
The frail people have very
unvaried, hardly any diversity
at all in the
bacterial communities.
So that suggests that diversity
in your microbial communities
is a good thing.
And indeed, if we look at
a lot of these diseases
where we see changes
in the microbiome,
we often see there's a reduction
in diversity, less variability.
So if you want to have
a healthy bacteria,
there is a way
that you can do it.
And it's basically eat
a really varied diet
because your diet is the
most important thing that
shapes your microbiome.
And they really like
really high fibre foods.
So lots of high fibre foods and
pulses are particularly yummy
for your microbiome.
But variable diet
is the key thing.
So just keep a little bit
of variation in your diet.
And remember, if you think back
to the checkpoint inhibitor
therapy, it was the patients who
had the high fibre diets that
were doing the best because
they have that more variable,
more robust community that's
more up to challenges.
So that's how your
microbiome could be
shaping your immune response.
But it's not just your internal
microbiome that might matter.
So you remember I said
let's do a little experiment
at the start?
OK.
So now is where you find
out about the microbiome
all around you.
Every time you move, you leave
a little microbial imprint.
What's left on there.
So when you all shook
each other's hands,
you exchanged some microbes.
When you spoke to each other,
you aerosolized some microbes.
Around 37 million microbes
per hour being aerosolized.
So we're actually in a massive
microbial soup right now.
Just breathe it in.
Come on.
And these microbes, we
still don't know that
much about the microbes
around, but they
could be really
important for our health.
So if we look at
something like an allergy,
there's been suggestions that
the urban microbiome might not
be as good for us as
the rural microbiome.
So could we be thinking about
the spaces that we're in
and thinking about
engineering those
by putting little
microbial bones in them?
So you could have your bright
and refreshing microbes
in your office so
you're all extra alert.
Because guess what?
The microbiome has been
shown to affect depression,
anxiety, concentration.
You could have the
freshen-up listing microbes.
Who knows?
It is being investigated.
It may sound nuts, but
this is being investigated.
The possibility
of bioengineering
microbiomes into our hospitals
and offices and workplaces.
So just watch the
space and just watch
those little aerosol
things in the corner.
You never know.
So that's the microbes
all around us.
But of course, it wouldn't
be me if I didn't just throw
in a few parasites, as well.
So let's get onto the parasites
because they really matter,
too, our long relationship
with parasites.
So I'm going to introduce you to
two of my favourite parasites.
It's just for Diane -
hookworm and whipworm.
So we're really imaginative
as parasitologists.
This is whipworm.
It looks like a whip.
And a hookworm hooks onto you.
These are little appendages,
so we call it hookworm.
They're not teeth,
although it is vampiric.
And it's a really mobile worm.
I don't know if it's going
to play if I do it here,
so I might go behind.
Oh, here it is.
So this is just
a larval hookworm
just wriggling
around on a slide.
So you can see just how mobile
those little critters are.
And they have a remarkably
intimate relationship
with the host.
So hookworms are about
the size of an eyelash.
And this is a hookworm in
the gut, wriggling around.
So the green stuff is the
villi of the small intestine.
And you can see it's wrapping
itself around a villi.
And you can see
little bits of red
suddenly appear
from time to time,
and that's because
it's vampiric.
It's having a little
drink of blood.
So what it does is it
fastens onto your gut wall,
has a tiny little
drink, and then pops off
and fastens on another way.
And that's actually a female.
I can see the eggs
in it's cavity.
Sorry.
I have no sensitivity
when it comes to worms.
I do have to warn you.
And then whipworm also
has a remarkably intimate
relationship with the host.
And it lives in the
large intestine.
I already talked a
little bit about it,
but I want you to really get
close to that whipworm now.
So I'm going to be showing
you a movie in a minute,
and you're going to be needing
those glasses that you've
been holding, and you're going
to be with the whipworms.
You're going to have a drive
through the large intestine
and see those whipworms
in their niche.
You all look fabulous.
You look so fabulous right now.
OK?
It looks much better
with the glasses on,
but you don't have
to have them on.
All right.
So this is not the 3D bit.
The next one is the 3D bit.
OK.
So now we're rotating
the large intestine.
A little bit fat on the outside.
You have quite a lot of fat
on your large intestine.
We're just going
to flip it around,
and now you're going to
enter the large intestine.
All those little funny
looking things are whipworms.
Really gives you a sense of
how much space they can take.
They're only about
two millimetres big.
OK.
And then we're just going
to remove the gut wall
now so that you can have
a closer look at the way
that they've tunnelled
their way through the gut.
So all those little wiggly bits
at the bottom are the head.
So the head, what it has to
do is to try and keep burrowed
into the lining of the guts.
And then its tail is
left free so it can mate.
Do you want to see it again?
OK.
I'll just go back and forward.
So now you can
just take your time
and just appreciate what
it's like to be a whipworm.
OK?
So we're going to flip it over.
So this is a imaging that we're
playing around with in the lab.
We're working with
material science.
This is X-ray
tomography, so this
is enabling us to
look into tissues
in three dimensions
for the first time,
really understand more
about these parasite niches.
So we're really learning now
a lot about this burrowing
behaviour that
the parasite does.
It's incredible, isn't
it, how intertwined it is?
So kinked.
It's quite incredible.
OK.
You can take the
glasses off now.
Sorry.
OK.
Now whipworm and hookworm
and other parasitic worms
have been around
for a long time.
And we've actually evolved
alongside these worms.
This is a picture from
Manchester Museum,
and this is them unwrapping
one of the mummies
that they have there, one
of the Egyptian mummies.
And when it was examined,
there was clear evidence
that this mummy had a parasitic
infection, parasitic worm
infection.
A lot of the ancient remains
that we found of man,
there's been evidence
of worm infection.
Even King Richard III had worms.
When they found his
body in the car park,
they found in his
gut cavity area,
they found evidence of
roundworm infection.
So they truly have
been around with us.
So our immune system has
evolved alongside these worms.
It's evolved to deal with them.
Now you may be slightly
relieved to know
that parasitic worms like
hookworm and whipworm
are actually very rare
now in the UK and lots
of parts of the world.
They're still remarkably common.
Around 2 billion
people still have them.
So does that mean
that now we've got rid
of these parasitic worms, our
immune response is tipped out
of balance because it's
used to having a worm in it,
because we always
used to have them?
Is there any evidence for this?
Well, you can go and
look at the evidence
where you can see there's still
worm infection or helminths.
So they are all the areas that
are coloured in red on the map.
And interestingly, when you look
all the area that are coloured
red and you compare them with
the incidence of autoimmune
disease, where your immune
response has gone wrong and is
attacking your body, there's
an inverse correlation.
You see something
similar for allergies.
So does this support the idea
that the immune response is out
of kilter?
Well, what happens if
you go to countries
where there's still worms?
So worms are a big problem.
Although they're
not always fatal,
they do cause big
problems, particularly
in school attendance because
they make you anaemic.
They make you very tired.
They cause a lot
of gut problems.
So there is a really big effort
to do mass deworming to improve
the health of populations.
So in countries like Kenya,
they've really taken to this.
And this is an
example where they're
deworming children in class.
They have to get
dewormed twice a year.
And then when they followed
up with these children
a few years, later
what they noticed
is the children were
starting to develop things
like eczema that had never been
seen in the population before.
Studies that looked
at pregnant women
also find something similar
because the parasites are quite
risky for pregnant women,
for the unborn child,
so it's important that
you treat these ladies.
So they compared what happened
to the babies of ladies
who've been treated
versus those that had not.
And the ones that
have been treated
tended to get more eczema,
evidence, again, of allergies.
And when you look at people
who've moved to the UK
from countries that
are wormy, that still
have the worms, what
you see is often
they complain that they've
developed allergies.
So when they moved to the UK,
they often develop allergies.
And when you look at
the second generation,
you see more allergies,
the third generation,
even more allergies.
So there is some
evidence to support it.
So does that mean that
what we really need to do
is put the worms back?
Now I told you that we're also
trying to get rid of worms.
Worms are not healthy.
They do make you unwell,
and some can even kill you.
And some people,
as I told you, also
have a really bad
immune response to them
and get really nasty
gut inflammation.
So it may not be
as simple as that.
However, it is being looked at.
There are clinical trials
taking certain types of worms
and giving them to people
to try and treat diseases.
And some of these trials
are remarkably effective,
particularly hookworm, that
nasty little vampiric parasite
that I showed you
is actually proving
quite effective at
treating some diseases.
But you have a very, very
low level of the parasite.
Some people who were
in clinical trials
actually named their parasites.
And they felt so
well they didn't want
to get rid of their parasites.
But as I said, parasites
do make you ill.
So should we be doing that?
And this is where it
gets really interesting
because as we understand
more about the immunology
with those parasites,
we know more about how
those parasites are interacting
with our immune system.
And what a lot of these
parasites are doing
is they're making vast
amounts of products,
kind of like parasite
vomit, I suppose,
which has really profound
effects on our immune cells.
And the reason
they're doing that
is because at the
end of the day,
we're their home and
their source of food,
and so they don't want
our immune response
to kick them out.
So it's in their interest
to try and calm down
that naughty immune response.
So what they do is
they can make things
that shut down the
immune response, that
regulate the immune response.
They can make some products that
stop the immune response being
warned that there's a parasite
there in the first place.
And now that we know
that and we know
which bits of that
bizarre parasite
vomit-- it's called
excretory-secretory product.
That's what's
actually called, yes--
that means that we can purify
certain bits of it that
have those properties
that we want
and use those to start
treating diseases
like autoimmune
disease or allergy.
So in the future, what
you might be doing,
is you might be popping into
the shop for your one-dose worm
therapy.
And on that note,
what I'd like to do
is thank all the
important people
who've done the bits
and bobs of my lab work
that I've shown you,
my collaborators.
So everybody in the Cruickshank
Collective and my collaborators
and the people who funded me.
But most of all, I want to
thank you and your parasites
for listening to me.
Thank you very, very much.
[APPLAUSE]
