How were using dogs to sniff out malaria James Logan
Malaria is still one of the biggest
killers on the planet.
Despite us making significant progress
in the last 20 years,
half the world’s population
is still at risk from this disease.
In fact, every two minutes,
a child under the age of two
dies from malaria.
Our progress has undoubtedly stalled.
Now we face many challenges
when it comes to tackling malaria,
but one of the problems that we have
is actually finding people who are
infected with malaria in the first place.
So, for example, if people have
some level of immunity to the disease,
then they can develop an infection
and become infectious and still pass it on
but not actually develop any symptoms,
and that can be a big problem,
because how do you find those people?
It’s like looking
for a needle in a haystack.
Now scientists have been trying
to solve this problem for some years,
but what I want to talk to you about today
is that the solution to this problem
may have been right under our noses
this whole time.
Now that was a bit of a heavy start,
with lots of really important statistics,
so I want us all
to just relax a little bit
and that’ll help me to relax
a little bit as well.
So why don’t we just all take
a nice deep breath in …
Wow. (Laughs)
And sigh,
and, whoo, going to get blown away there.
OK, now I want you to do it again,
but this time, I want you to do it
just through your nose,
and I want you to really sense
the environment around you.
And in fact, I want you to really smell
the person who’s sitting next to you.
Even if you don’t know them, I don’t care.
Lean in, get your nose
right into their armpit,
come on, stop being so British about it,
get your nose into the armpit,
have a good old sniff,
see what you can smell.
(Laughter)
Now each and every one of us
would have had a very different
sensory experience there.
Some of us would have smelled
something rather pleasant,
perhaps somebody’s perfume.
But some of us might have smelled
something a little bit less pleasant,
perhaps somebody’s
bad breath or body odor.
Maybe you even smelled your own body odor.
(Laughter)
But, you know, there’s probably
a good reason
that some of us
don’t like certain body smells.
Throughout history,
there have been many examples of diseases
being associated with a smell.
So, for example, typhoid apparently
smells like baked brown bread,
and that’s quite a nice smell, isn’t it,
but it starts to get a little bit worse.
TB smells like stale beer,
and yellow fever smells like the inside
of a butcher shop, like raw meat.
And in fact, when you look
at the sort of words that are used
to describe diseases,
you tend to find these words:
“rotting,” “foul,” “putrid” or “pungent.”
So it’s no surprise, then,
that smell and body odor
gets a bit of bad reputation.
If I was to say to you, “You smell,”
now, you’re going to take that
not exactly as a compliment, are you.
But you do smell.
You’ve just found that out. You do smell.
It’s a scientific fact.
And I’d quite like
to turn that on its head.
What if we could actually
think about smell in a positive way,
put it to good use?
What if we could detect the chemicals
that are given off
by our bodies when we’re ill,
and use that to diagnose people?
Now we’d need to develop good sensors
that would allow us to do this,
but it turns out that the world’s
best sensors actually already exist,
and they’re called animals.
Now animals are built to smell.
They live their everyday lives
according to their nose.
They sense the environment,
which tells them
really important information
about how to stay alive, essentially.
Just imagine you’re a mosquito
and you’ve just flown in from outside
and you’ve entered this room.
Now you’re going to be entering
a really complex world.
You’re going to be bombarded
with smells from everywhere.
We’ve just found out
that we’re really smelly beasts.
Each one of us is producing
different volatile chemicals.
It’s not just one chemical, like BO –
lots and lots of chemicals.
But it’s not just you,
it’s the seats you’re sitting on,
the carpet, the glue that holds
the carpet to the floor,
the paint on the walls, the trees outside.
Everything around you
is producing an odor,
and it’s a really complex world
that the mosquito has to fly through,
and it has to find you
within that really complex world.
And each and every one of you will know –
Come on, hands up, who always
gets bitten by mosquitoes?
And who never gets bitten?
There’s always one or two really
annoying people that never get bitten.
But the mosquito
has a really hard job to find you,
and that’s all to do
with the way you smell.
People who don’t attract
mosquitoes smell repellent,
and what we know is that –
(Laughter)
I should clarify, repellent to mosquitoes,
not to people.
(Laughter)
And what we know now
is that that is actually
controlled by our genes.
But mosquitoes are able to do that
because they have
a highly sophisticated sense of smell,
and they’re able to see through
all the, sort of, odor sludge
to find you, that individual,
and bite you as a blood meal.
But what would happen
if one of you was infected with malaria?
Well, let’s just have a quick look
at the malaria life cycle.
So it’s quite complex,
but basically, what happens is a mosquito
has to bite somebody to become infected.
Once it bites an infected person,
the parasite travels
through the mouth part into the gut
and then bursts
through the gut, creates cysts,
and then the parasites replicate,
and then they make a journey from the gut
all the way to the salivary glands,
where they are then injected
back into another person
when the mosquito bites,
because it injects saliva as it bites.
Then, inside the human,
it goes through a whole other cycle,
a whole other part of the life cycle,
so it goes through
a liver stage, changes shape,
and then comes out
into the bloodstream again,
and eventually, that person
will become infectious.
Now, one thing we know
about the parasite world
is that they are incredibly good
at manipulating their hosts
to enhance their own transmission,
to make sure that they get passed onwards.
If this was to happen
in the malaria system,
it might make sense
that it would be something
to do with odor that they manipulate,
because odor is the key.
Odor is the thing that links us
between mosquitoes.
That’s how they find us.
This is what we call the malaria
manipulation hypothesis,
and it’s something that we’ve been
working on over the last few years.
So one of the first things
that we wanted to do in our study
was to find out whether
an infection with malaria
actually makes you more attractive
to mosquitoes or not.
So in Kenya, with our colleagues,
we designed an experiment
where we had participants,
children in Kenya, sleep inside tents.
The odor from the tent was blown
into a chamber which contained mosquitoes,
and the mosquitoes would
behaviorally respond.
They would fly towards
or fly away from the odors,
depending on whether
they liked them or not.
Now some of the participants
were infected with malaria,
and some of them were uninfected,
but importantly,
none of the children
had any symptoms whatsoever.
Now when we found and saw the results,
it was really quite staggering.
People who were infected with malaria
were significantly more attractive
than people who were uninfected.
So let me explain this graph.
We have “number of mosquitoes
attracted to the child,”
and we have two sets of data:
before treatment and after treatment.
On the far left-hand side,
that bar represents
a group of people who are uninfected,
and as we move
towards the right-hand side,
these people have become infected
and they’re moving towards the stage
that they’re infectious.
So right at the stage
when people are infectious
is when they are
significantly more attractive.
In this study, then, what we did
is we obviously gave
the children treatment
to clear the parasites,
and then we tested them again,
and what we found was that highly
attractive trait that was there
disappeared after they had
cleared the infection.
So it wasn’t just that the people
were more attractive,
it was that the parasite
was manipulating its host in some way
to make it more attractive to mosquitoes,
standing out like a beacon
to attract more mosquitoes
so that it could continue its life cycle.
The next thing we wanted to do
was find out what it was
the mosquito was actually smelling.
What was it detecting?
So to do that, we had to collect
the body odor from the participants,
and we did this by wrapping
bags around their feet,
which allowed us to collect
the volatile odors from their feet,
and feet are really important
to mosquitoes.
They really love the smell of feet.
(Laughter)
Especially cheesy feet.
Anybody got cheesy feet back there?
Mosquitoes love that smell.
So we focused on the feet,
and we collected the body odor.
Now when it comes to mosquitoes
and olfaction, their sense of smell,
it’s very complex.
It would be really nice if there was
just one chemical that they detected,
but it’s not that simple.
They have to detect a number of chemicals
in the right concentration,
the right ratios,
the right combinations of chemicals.
So you can sort of think about it
like a musical composition.
So, you know, if you get the note wrong
or you play it too loud or too soft,
it doesn’t sound right.
Or a recipe: if you get
an ingredient wrong
or you cook it too long or too little,
it doesn’t taste right.
Well, smell is the same.
It’s made up of a suite of chemicals
in the right combination.
Now our machines in the lab
are not particularly good
at picking out this sort of signal –
it’s quite complex.
But animals can,
and what we do in my laboratory
is we connect microelectrodes
to the antennae of a mosquito.
Imagine how fiddly that is.
(Laughter)
But what we also do is connect them
to individual cells within the antennae,
which is incredible.
You don’t want to sneeze
when you’re doing this,
that’s for sure.
But what this does is it allows us
to measure the electrical response
of the smell receptors in the antennae,
and so we can see
what a mosquito is smelling.
So I’m going to show you
what this looks like.
Here’s an insect’s cell,
and it will respond in a second
when I press this button,
and you’ll see it sort of ticking over
with this response.
An odor will be blown over the cell,
and it will go a bit crazy,
sort of blow a raspberry,
and then it will go back to its resting
potential when we stop the odor.
(Rapid crackling)
(Low-pitch crackling)
(Rapid crackling)
OK, there we go,
so you can go home now and say
that you’ve seen an insect smelling
and even hearing an insect smelling –
it’s a weird concept, isn’t it?
But this works really well,
and this allows us to see
what the insect is detecting.
Now using this method
with our malaria samples,
we were able to find out
what the mosquito was detecting,
and we found the malaria-associated
compounds, mainly aldehydes,
a group of compounds that smelled,
that signified the malaria signal here.
So now we know
what the smell of malaria is,
and we’ve used the mosquito as a biosensor
to tell us what the smell
of malaria actually is.
Now I’d like to imagine
that you could, I don’t know,
put a harness on a little mosquito
and put it on a lead and take it out
and see if we can sniff people
in a community –
that goes on in my head –
and see whether we could
actually find people with malaria,
but, of course,
that’s not really possible.
But there is an animal
that we can do that with.
Now dogs have an incredible
sense of smell,
but there’s something
more special about them:
they have an ability to learn.
And most of you people will be
familiar with this concept at airports,
where dogs will go down a line
and sniff out your luggage or yourself
for drugs and explosives
or even food as well.
So we wanted to know,
could we actually train dogs
to learn the smell of malaria?
And so we’ve been working with a charity
called Medical Detection Dogs
to see whether we can train them
to learn the smell of malaria.
And we went out to the Gambia
and did some more odor collection
on children that were infected
and uninfected,
but this time, we collected their odor
by making them wear socks,
nylon stockings,
to collect their body odor.
And we brought them back to the UK
and then we handed them to this charity
to run the experiment.
Now I could show you a graph
and tell you about that experiment works,
but that’d be a bit dull, wouldn’t it.
Now, they do say never work
with children or animals live,
but we’re going to break that rule today.
So please welcome onto the stage Freya …
(Applause)
and her trainers Mark and Sarah.
(Applause)
Of course, this is
the real star of the show.
(Laughter)
OK, so now what I’m going to ask is
if you can all just be a little bit quiet,
not move around too much.
This is a very, very strange
environment for Freya.
She’s having a good look at you guys now.
So let’s stay as calm as possible.
That would be great.
So what we’re going to do here
is basically, we’re going to ask Freya
to move down this line
of contraptions here,
and in each one of these
contraptions, we have a pot,
and in the pot is a sock that has been
worn by a child in the Gambia.
Now three of the socks have been worn
by children who were uninfected,
and just one of the socks was worn
by a child who was infected with malaria.
So just as you would see an airport,
imagine these were people,
and the dog is going to go down
and have a good sniff.
And let’s see if you can see
when she senses the malaria,
and if she senses the malaria.
This is a really tough test for her
in this very strange environment,
so I’m going to hand it over now to Mark.
(Laughs) Number three. OK.
(Applause)
There we go.
I didn’t know which pot that was in.
Mark didn’t know.
This was a blind test, genuinely.
Sarah, was that correct?
Sarah: Yes.
JL: That was correct. Well done, Freya.
That is fantastic. Whew.
(Applause)
That is really wonderful.
Now Sarah is going to actually change
the pots around a little bit,
and she’s going to take
the one with malaria away,
and we’re just going to have four pots
that are containing socks from children
that had no malaria,
so in theory, Freya should go
down the line and not stop at all.
And this is really important,
because we also need to know
people who are not infected,
she needs to be able to do that.
And this is a tough test.
These socks have been in the freezer
for a couple of years now,
and this is a tiny bit of a sock as well.
So imagine if this was a whole person,
giving off a big signal.
So this is really incredible.
OK, over to you, Mark.
(Laughs)
(Applause)
Brilliant. Fantastic.
(Applause)
Really super. Thank you so much, guys.
Big round of applause
for Freya, Mark and Sarah.
Well done, guys.
(Applause)
What a good girl.
She’s going to get a treat later.
Fantastic.
So you’ve just seen that
for your own eyes.
That was a real live demonstration.
I was quite nervous about it.
I’m so glad that it worked.
(Laughter)
But it is really incredible,
and when we do this,
what we find is that these dogs
can correctly tell us
when somebody is infected with malaria
81 percent of the time.
It’s incredible.
92 percent of the time,
they can tell us correctly
when somebody does not have an infection.
And those numbers
are actually above the criteria
set by the World Health Organization
for a diagnostic.
So we really are looking
at deploying dogs in countries,
and particularly at ports of entry,
to detect people who have malaria.
This could be a reality.
But we can’t deploy dogs everywhere,
and so what we’re also looking to do
and working on at the moment
is the development of technology,
wearable tech that would
empower the individual
to allow them to self-diagnose.
Imagine a patch that you wear on the skin
that would detect in your sweat
when you’re infected with malaria
and change color.
Or something a little more
technical, perhaps:
a smartwatch that would alert you
when you’re infected with malaria.
And if we can do this digitally,
and we can collect data,
imagine the amount of data
that we can collect on a global scale.
This could completely revolutionize
the way that we track
the spread of diseases,
the way that we target our control efforts
and respond to disease outbreaks,
ultimately helping to lead
to the eradication of malaria,
and even beyond malaria,
for other diseases
that we already know have a smell.
If we can harness the power of nature
to find out what those smells are,
we could do this and make this a reality.
Now, as scientists, we’re tasked
with coming up with new ideas,
new concepts, new technologies
to tackle some of the world’s
greatest problems,
but what never ceases to amaze me
is that often nature
has already done this for us,
and the answer …
is right under our nose.
Thank you.
(Applause)