Hi, I am Toto Olivera.
I am a professor at the
University of Utah.
And I would like to tell you about
venomous cone snails.
So, you've heard about predators.
And it is seldom
that you
think of a snail
as a predator.
You think of snails
that are crawling around
in your garden.
But I am going tell
you about a special group
of snails called cone snails.
And they are predators.
And predators vary
from those that use
mechanical strategies
such as a great white shark.
You have to be able to swim fast
and have great teeth
if you are a white shark.
To predators that have
a mixed mechanical
and chemical strategy
such as the Komodo dragon,
which has very strong jaws
but nevertheless it
has secretions that allow
it to help capture its prey.
To the cone snails, which are
in fact predators as well,
but they use
a purely chemical strategy,
and that makes them
fairly unique as predators.
So there are 700 different
types of cone snail species,
and all of them
are predatory.
All of them are
venomous. And each species
has fairly specific prey.
Some cone snails prey on fish.
Some cone snails
prey on marine worms.
And some cone snails
prey on other snails.
All of them live
in the tropics,
in the oceans
from very shallow water
to really deep water.
And the most unusual
kinds of snails
are those that hunt fish
becuase they not only
are successful hunters of fish,
but a few species
are dangerous to man
and can kill people.
And Conus geographus
which is the snail in the
center, the large snail
in the center,
kills people
with a 70% fatality rate.
So if you get stung
by this snail
and you have no medical attention,
you have a 70%
probablility of dying.
Let me show you
what the cone snails
do to catch fish.
So when a cone snail
sniffs a fish,
it extends
its distensible proboscis
as you see here,
and this particlular species
goes for a region
of the fish
called the lateral line
which is lots of nerves,
and what you can see
is the snail
beginning to
approach the fish,
and when it touches
the skin of a fish
then from the proboscis
out comes a harpoon like tooth
which is both harpoon
and hypodermic needle.
And so what you see
is the tooth extended,
and the venom flows from
the proboscis
to the tooth
and at the end of the tooth
is a hole
because it's hollow,
and so when this tooth
gets injected into a fish
the venom flows
into the body of the fish
and at the same time
it is speared,
because in fact the end of the tooth
is shaped like a harpoon.
So once the snail
touches the skin of a fish
it then can inject its venom,
and the effects
are what you are going to see here.
It tethers the fish,
and now it can
draw the fish into
its false mouth,
and in this case
in about an hour and a half
it will regurgitate
the scales and bones
of the fish
as well as the one
harpoon that it used
for injecting the venom
into the fish.
And so what you can see is
the fish
is immobilized
and now the snail
can completely
engulf the fish
in this false mouth
and predigestion
takes place
so that all the hard
parts get regurgitated
but the soft parts
of the fish go further down
into the digestive tract.
And what you can see
is that the
fish has very, very stiff fins
and that is one of the
effects of the venom
to cause this
so-called tetanic paralysis.
All cone snails
have the same
venom apparatus.
They have an organ
filled with harpoons
that are in various
stages of assembly
which is a quiverlike organ,
and when they go hunting
they move one
of the harpoons
to the tip of
their proboscis
and they use it
only once.
And the venom is actually
made in this long duct
and it is pushed out
by the muscular bulb
and as a result
this is an efficient way
to inject venom
into the prey.
So the snails
in effect
have evolved the
equivalent of disposable
hypodermic needles
for injecting
their venom into their prey.
Here is another snail
that is hunting
snails instead of fish.
And it is going to
inject its venom,
and when it injects
its venom,
you can see that the
behavior of the prey
snail changes
immediately.
And so because
the venom has this
effect on the snail,
the snail can't
move away,
and at the same time
it can't go into its shell.
And so now the predator
can eat it at its leisure.
What is interesting
about snail hunting cones
is they usually
have to harpoon
their prey many times
and that is so that
the muscles that
attach the snail
to the shell
become relaxed
and its easier
to pick out the snail.
This shows you
a video that really
shows how
fast the immoblization
can be with a good strike.
And this is real time.
And you can see
the fish is instantly
immobilized.
And this also shows you
an interesting thing
that was completely
unexpected.
As the snail begins
to engulf the fish
what you are going to
see is that
the fish in fact recovers
and so sometimes
the venom is effective,
but there are lapses.
And so you see
the fish recovers there.
In this case of course,
there is no biological effect
because the snail
has already completely
engulfed the fish.
But once in awhile,
you see these fish escape.
And under those conditions
the snail always does a search
for the paralyzed fish.
Here is another strategy
for catching fish.
This is another
group of cone snails.
These guys
when they are close
to a fish they open
their mouth,
and this species,
the Tulip Cone,
has frills at the end
of its mouth
and what they do
is they always engulf
the fish first,
and only when they have
englufed the fish
do they harpoon
their prey.
And so it's a different way
of catching a fish.
We call this
the "net strategy".
So how do you study
how these venoms act?
And one of the ways
to do it
is to purify
the different components
of the venom.
And you need an assay for that.
So at the beginning
of our work, we were
interested in the
components of the venom
that potentially
could kill people
because they cause paralysis.
And so our assay
was to use mice
and what we would do
is we would put mice
upside down on a
wire screen
and inject different
fractions of the venom
and some fractions
had no effect at all
in fact, most fractions,
but a few fractions
caused the mouse
to start to be paralyzed
and if it is paralyzed
it can't clench
its paws
and hang on
to the wire screen
and so it would fall.
So what we did was we just
characterized and purified
those components
that made the mouse fall
and that way we isolated
using this assay,
the first two components
of the venom
and these are their structures
And we were surprised to find
that the active
components of the venom
are like very small
proteins called peptides.
And so the first peptide
that we isolated
acts very much like
cobratoxin
or bungarotoxin
from snakes.
And the second
peptide we isolated acts
very much like
the deadly toxin
that you have
in pufferfish.
And so when you get
stung by one of these
snails, these Geographus cones,
it's equivalent
to being bitten by
a cobra
and eating a lethal dose
of pufferfish
at the same time.
And these are the chemicals
that really cause that.
They are small proteins.
with the sequences
that you can see here.
Then our whole research
outlook changed
because a young undergraduate,
an 18 year old kid,
came into the lab
and he said, you know, you guys
have been injecting the mice
directly in their body cavity.
I really think
that it would be better
if you injected mice
directly
into their central nervous system.
And I wasn't so persuaded
by this, but the great thing
about being at a University
is the students do
what they want.
They don't necessarily
follow the professor's advice.
And that really is
the source of a lot of
creativity
of the research in universities.
And so what this kid found
was that if he injected directly
into the brain
of a mouse,
that each component
of the venom
and each peak
here is one component
of the venom
caused a different
kind of behavior
in the mice.
So while there were some
components that
paralyzed mice
other made them jump
and twist as they are jumping.
Others made them uncoordinated.
And this major peak
that I am showing you here,
it put mice to sleep
and we were just amazed
becuase the mice
would go to sleep
and 12-24 hours later
they'd be perfectly fine,
but that was only true
if the mice were under three weeks of age,
If they were over three weeks of age
then instead of going to sleep
they would climb the sides of their cages
and run from corner to corner.
And then other peptides made
mice drag their back legs
or run around in circles
or swing their heads
back and forth
or kick on their
back and stretch
or scramble or scratch
and convulse.
And so the remarkable thing
was that all of this stuff
was found in one venom.
And so that tells us that
the venoms of these
snails were
extremely complex
with lots and lots
of bioactive things.
And so we have been trying to figure
this out ever since.
So why are there so
many peptides?
And it turns out
that some peptides
are used to capture prey,
some peptides
are used to defend themselves
agains predators
and some are to deter
competitors.
And so every species
of cone snail has a set
of biological interactions.
And each species is different.
So a different Conus species
would have different prey,
different predators
and different competitors.
In other words, each species
has its own
particular ecological niche
and so the venom
components are essentially
mutated
as species evolve
so that each is very fit
for its own particular
ecological niche.
So the study of cone snails
and specifically this one
led to the isolation
of one of these venom components
that turned out to have
a use that we never expected.
Today, that venom
component
is an approved drug
for very severe pain.
And so when your pain
is so severe
that even morphine doesn't help
then the component
of this cone snail venom
can help you in a lot of cases.
So this was
really unexpected
that by studying this very
seemingly esoteric
group of snails
we were able to
end up with
a drug for pain
that now is used
by people
in very severe pain.
Thank you very much.