[Applause]
so my aim today is to convince you that
this animal is a source of life saving
human therapeutics now those of us that
live in Australia will be well aware
that we are literally surrounded by
venomous animals right but in fact
venomous animals are replete throughout
the entire world because about 15% of
all animal species on the planet are
actually venomous things like venomous
spiders bees ants and wasps are common
in suburban backyards right around the
world and they're all completely
venomous some are more exotic like
assassin bugs which interestingly we
find to be very prevalent in the local
cemetery rather ironically a bit more
uncommon but we find these animals all
the way around the world and if those of
us that live in Queensland know there's
no escaping these venomous animals when
we venture into the ocean because
there's plenty of venomous marine
animals as well right octopus sea
anemones jellyfish stingrays venomous
snails that we'll talk about later and
for the first fun fact of the day did
you know that many corals are actually
venomous corals are actually closely
related to sea anemones and jellyfish
and they used the exact same type of
stinging cells known as the meta sites
to deliver their venom and capture prey
so why do we have so many venomous
animals in on the planet and the reason
is the position of Venom's transforms
the act of capturing your prey from a
physical battle to chemical warfare and
what that enables you to do is capture
prey that's much bigger than you that's
potentially dangerous or was just more
mobile than you so this little crab
spider here is killing a bee that is not
only much larger than the spider but it
has the potential to fly away so why can
it do that because it has venom that
will rapidly immobilize that so it can't
escape perhaps the most bizarre use of
venom oh are these marine cone snails
these are slow-moving snails that live
at the bottom of the ocean and
remarkably many of them prey on fish so
how do these slow-moving cone snails
capture fish this sounds like something
out of science fiction but what they do
is they take venom and they load it into
minuscule harpoons and they actually
shoot it at the fish and that
instantaneously paralyzes the fish and
they're just reel it in and eat it it's
quite remarkable
now some venomous animals are dangerous
to us and snakes of the prime example
but no venomous animal has evolved to
kill us and what that means is the vast
majority of venomous animals aren't
actually harmful to humans and a classic
example is the world's biggest spider
the Goliath tarantula this hasn't been
photoshopped this is the real size these
spiders can get as large as a dinner
plate and yet like all tarantulas
they're completely harmless to humans
they pose no threat to us at all and the
other thing we have to remember is that
all of these venomous animals play
really important roles in their own
ecosystems which brings me to the second
fun fact of the day and that is that
spiders make up 25 million tons of the
Earth's biomass and each year they eat
more tons of insect prey than the entire
human population eats in meat and fish
every year that's a lot of insects we'd
probably be suffering from an insect
apocalypse if it wasn't for these
spiders eating these insects every
single day so what is in these Venom's
what compounds do we find in there when
I started looking this 20 years ago I
had no idea and naively I thought well
these secretions are probably not very
complicated why does the spider need
more than a few insecticidal compounds
to kill its prey but how wrong I was
what I'm going to show you is the very
first experiment from 20 years ago that
I ran to try and explore what was in the
venom of the infamous Australian
funnel-web spider and this is a process
that separates the venom components
according to whether they're very water
soluble or not so water soluble and the
water soluble compounds come out first
and I was expecting a couple of peaks
and this is what I found the Peaks just
kept coming
and coming and coming and coming they
weren't a few compounds they weren't a
few dozen compounds they were in fact
hundreds of compounds at least in the
venom of this spider and the amazing
thing was the ones that came out first
that were very water-soluble were small
molecules things like amino acids and
neurotransmitters but all the rest were
small proteins or peptides about the
size of human insulin and what we now
know quite remarkably is the venom of
the Australian funnel-web spider
contains more than three thousand
different peptides we think it may be
the most complicated chemical Arsenal in
the entire natural world so given that
these Venom's are so complex have so
many molecules in there the obvious
question is can any of them be a benefit
in terms of treating human disease and
the unequivocal answer is yes we already
have six drugs that have been derived
from Venom's and I'm going to do
examples of two of them the first one is
the very first ever venom derived drug
and it comes from a deadly snake it
comes from a Brazilian Viper called
bothrops Jerrica and what clinicians
notice is when people came into the
hospital that had been invented mated by
the spider that they were suffering from
a precipitous drop in blood pressure and
some smart people at squid
pharmaceuticals said what if we could
work out what the molecule was that
caused a decrease in blood pressure
maybe that would be useful for people
with high blood pressure and they did
isolate that molecule it was a small
peptide they made a few changes and it
became the world's first blockbuster
antihypertensive drug and all modern
antihypertensive drugs are derived from
that molecule from that snake
so that snake has certainly killed some
people but the drug that we've got out
of its venom has saved many more lives
than that
the second example is a more recent one
I like to give just because I think this
is a beautiful lizard it's an
anti-diabetic drug derived from the
venom of the beautiful Gila monster
lizard this is a small peptide it's a
very successful anti-diabetic drug and
the point I want to make with this one
is that human chemists tried to take
this peptide and make changes and make
it better and tried a whole bunch of
things but the drug that they ended up
with was exactly the same molecule but
in the venom of the Liz
they couldn't be the evolution that had
gone on in creating that venom so that
you Xena tied the drug by a toe is the
exact same molecule that you would find
in the venom of this lizard so want to
talk a little bit now about the sort of
work that's going on here at the
University of Queensland specifically in
my lab in this area we use Venom's to
inspire the development of drugs to
treat nervous system disorders and the
particular disorder I want to talk about
today stroke I think we've all been
touched by somebody in our family or
circle of friends who has suffered a
stroke it is after all the second
largest killer of people in the world
it's the third largest course killer in
Australia it's actually also the primary
course of long term disability and the
reason for those I'm sure you all know
is that stroke causes brain damage so
one year after a stroke 50% of survivors
still require daily care because of the
disability they've suffered as a result
of the stroke and the problem is we have
no therapeutic options for these people
we have no drugs to prevent the brain
damage after stroke not a single one so
there are two types of stroke there is a
hemorrhagic stroke which is a bleed in
the brain and for that there's no drugs
at all or we can use you're at the mercy
of what happens to your brain the other
type of stroke is an ischemic stroke
where there's a clot in the artery
leading to the brain and for that we
have one drug called TPA it's a clot
busting drug in an attempt to remove
that clot the problem is it can't be
used in hemorrhagic stroke it would make
the situation worse and even in ischemic
stroke it could induce potentially an
intracranial hemorrhage so neurologists
are scared of it they don't like to use
it and the reality is that only 5% of
all stroke patients worldwide get this
stroke so most stroke patients get no
drugs at all it's quite remarkable so
what happens in a stroke what is that
we're trying to to sort of develop a
drug to prevent so there's a clot in the
artery and what that does is lead to a
lack of blood supply to that region of
the brain and the lack of oxygen the
core region that's affected the so
called ischemic core the dogma what is
taught to medical students is that that
part of the brain will die pretty much
instantaneously
and you're never going to recover that
not therapeutically recovery will forget
about the ischemic call but there's a
spreading wave of destruction out from
that ischemic call that evolves over
hours today so it's flow evolution and
the forties if you had a good drug you
might be able to minimize this so called
Perry in fact zone and so that's what
we've been trying to do so what happens
biochemically in a stroke so you've got
decrease blood supply to the brain a
lack of oxygen and because of that the
brain has to change the way it utilizes
its fuel and some of you probably know
that the brain is the biggest user of
glucose in your body it consumes huge
amounts of glucose cause nerve cells are
really energy hungry but it can't burn
the glucose the way it would like to it
has to revert instead to an ancient
metabolic pathway called glycolysis and
the end product of glycolysis is
something called lactic acid it's the
same thing that happens in your muscles
when you're working really hard so
you're running your muscles can't get
oxygen hard enough they also use it
pathway you end up with lactic acid
that's what causes the pain in your
muscle but of course your muscle can
clear it your brain in a stroke can't
clear that lactic acid so your brain
actually becomes acidic the pH of your
brain goes down so you get what's called
brain acidosis
and unfortunately at the end of your
neurons those little red dots are drawn
at the end of the neuron there there's
an ion channel called acid sensing ion
channel one a a horrible name
or just a zig one a so iron channels are
things that sit in the membranes of your
neurons and they let ions in and out
sodium potassium calcium this one sits
at the end of your nerves and it detects
changes in pH so when your brain becomes
acidic after the stroke it activates
that channel that channel turns on and
unfortunately what that channel then
does is send a signal to that neuron
that says die and so the neuron dies as
a result of the activation of that
channel so we had a very simple idea
based on the work of ours and others and
that is what if we could find a molecule
that stopped that channel being
activated in the
context of stroke could we prevent the
brain damage downstream of that
activation of course what we needed
though was a guerilla potent inhibitor
of that channel something that inhibited
that channel really well and we turned
to Venom's
why Venom's we work with neurotoxic
venom that target the nervous system of
their prey and therefore of molecules
therefore the tag of these ion channels
they're their best known natural source
of these ion channel modulators now the
University of Queensland we had the
largest collection of Venom's in the
world venom from over 700 species of all
types of venomous animals from all
around the world so the winning molecule
in this context could have come from
anywhere but I'm delighted to say the
winning molecule came from a local
spider the winning molecule came from
the Fraser Island funnel-web spider
those of you watching from overseas
Fraser Island is the biggest sand island
in the world found a couple of hours to
the north of Brisbane and has a
population of these funnel-web spiders
and the molecule we found in that spider
I've shown the three-dimensional
structure here being animated
we call hi1 a it's about one-and-a-half
times the size of human insulin now when
we started this project we knew there
was one small molecule that inhibited
that channel was an anti diuretic drug
called a Milla right and this peptide
that we isolated from the Fraser Island
funnel-web spider inhibits the channel
with 20,000 fold higher potency than
that small molecule drug it's an
extraordinarily potent selective
inhibitor of that as a guano channel and
so we had the molecule we needed to test
our hypothesis does this molecule
prevent me after stroke and so the
experiment I've shown you here is where
rats after a stroke are either not
treated or they given this molecule two
hours after the stroke and what those
bars are showing you there is the
infarct size or the amount of brain
that's died effectively and if you
compare the red bar the animals that
didn't get the hi1 a peptide from the
spider and the green ones that did you
can see we've reduced the brain damage
by over 80
she's remarkable so then we tried we
said what happens if we deliver the drug
four hours after stroke that's an
important number because that's the
longest time at which the current drug
can be delivered and 60% of people take
more than two hours to get to the
hospital and you can see even when we
give the drug four hours after the
stroke begins we still can reduce the
brain damage by almost 90% so then we
went into completely uncharted territory
eight hours which is twice the longest
time at which you can give the current
drug that's about all the only one and
even at eight hours we still were able
to reduce the brain damage by 65% now
this data is the peri in fact zone the
zone that I told you at the beginning
should be therapeutically recoverable
and I think this should prove that it is
recoverable but what about this scheme
you call remember the dogma is schema
core it's going to die straightaway
you're not going to be recover it this
is what happens in this scheme we call
we still see reduction in brain damage
in the ischemic core so we believe that
Dogma is wrong we believe that if you
have a good drug you can actually
protect that part of the brain as well
which is really exciting
the other thing we wanted to look at is
it's what we want to do is have a drug
that will both enable more people to
survive a stroke but give them better
quality of life afterwards we went and
looked at the neurological performance
of the mice and their motor performance
that is their muscular activity
now this neurological score is a
composite score of watching them to do
various activities and a score of zero
means these are perfectly happy happy
rats that do normal things and a score
of six means they're essentially
paralyzed and incapable of doing
virtually anything and you can see 72
hours after the stroke these rats are
severely impaired so this is what
happens to the rats though that got the
drug two hours after the stroke almost
back to normal
the neurological function is retained
despite the fact that they've suffered a
stroke so then we looked at their motor
coordination and to do that we get them
to walk down a little narrow beam into
the nest and rodents are really good at
balancing and climbing so you can see
before the stroke they never did that
wrong way they all never fall off the
beam but 72 hours after the stroke the
untreated rats are falling off almost
every time they've completely lost their
motor coordination
and this is what happens to the rats
they've got the drug two hours after the
stroke you can see gain we've almost
normalized their motor coordination
these are very happy we'll coordinated
rats which is very exciting so why do we
think this potentially could be a very
important breakthrough in the stroke
field
well the first thing is this is not a
clot busting drug there's no risk of it
inducing bleeding and therefore it
should be okay to be given to him
erratic stroke patients why is that
important because at the moment you
can't treat a stroke patient until you
get to the hospital and image their
brain because you must know whether it's
a hemorrhagic on the skin explode
because it's a hemorrhagic stroke you
can't do anything you can only get the
drug up it's a scheme but this drug you
can give it to any stroke patient and
the important thing about that is it
means that first responders might be
able to deliver it why is that important
because once the stroke starts you lose
two million neurons per minute so the
sooner you can get a drug in there that
protects the brain the better the
outcomes going to be for that patient
the other thing that's important is
we've shown there's a very long
treatment window remember I told you we
even got an effect eight hours after
stroke this is very important for areas
like Queensland that are huge and and
not very densely populated so if you're
on a regional area or perhaps you're in
the Torres Strait region of Australia
and you've got to get to a hospital in
the mainland that can take five or six
hours and what we're showing is even if
it does take that long
then you're going to get some benefit
from the stroke so it's going to be
really important for people in regional
areas and the really interesting new
discovery we made just recently is we
asked the questionable since this
channel is really important in a
skimming injury of the brain is it
important for skimming injury of other
organs that is in injuries due to lack
of oxygen and the the organ that's most
susceptible to that aside from the brain
is the heart and we found that the
molecule also protects the heart muscle
cells from ischemic injury so it may
have applications in heart attack
cardiac arrest and in fact maintaining
the integrity of donor hearts that are
going to be transplanted as well so I
want to end with the final fun fact of
the day which I hope by now you're all
going to agree with and that is the
venomous animals
right they for the most part pose no
threat to humans but even those that do
can provide life-saving drugs and we saw
that with that venomous Viper that
bothrops Jerrica that led to that
antihypertensive drug so as I stood at
the beginning rather than vilifying
venomous animals I think we should learn
to admire them and as this gentleman
shows us respect them as well
[Applause]