The power of venom and how it could one day save your life Mand Holford
How does a sea snail catch a fish?
I mean, it’s a snail, so it’s slow,
and the fish is not.
But yet, this happens.
Hidden under the sand is a cone snail.
And that orange thing you see
is kind of like a tongue.
We call it a proboscis.
It uses that to track and subdue
this unsuspecting fish.
In this predator-prey interaction,
these are clearly not
your garden variety escargots.
These are assassins of the sea.
And their weapon of choice is venom.
Venom, like the venom you find
in venomous snakes and scorpions,
these sea snails, they use their venom
to subdue fish, worms
and other snails.
And the venom of these snails,
it’s not just one thing,
it’s actually a cocktail
of toxic molecules
that are packaged and delivered
through a false tooth called a radula.
You can think of the radulas
as hypodermic needles.
Now, no need to worry,
these snails are practicing
good needle habits,
because each radula is only used once.
Now from your own knowledge
about venomous organisms,
and the keep-you-up-at-night
fish-killing video that I just showed you,
you might think that venom
is dangerous and all bad.
Well, yes and no.
A more accurate way of thinking of venom
is to think of it as both
a supervillain and a superhero.
In my lab, we study the evolution
of venom in these sea snails
as a force for good.
Sounds like a stretch,
or maybe even snake oil,
but actually,
while there are snakes involved,
the product is legit.
One reason the venom product
is so successful
is that it transforms a physical warfare
into a biochemical one.
Where usually the predator-prey
interaction is one of brute force,
venom takes it to a molecular scale.
And it’s not size that matters,
but the mixture of your venom arsenal.
The chemistry of the toxins
in your arsenal
is what’s going to enable David
to conquer Goliath.
And in our scenario,
David is clearly the snail.
Another feature of venom
that makes it so successful
is that the toxins work
with the precision of a Swiss Army knife.
And so these toxins,
they come for strongholds
that help an organism to function.
So they target blood, brain and membranes.
Whether it’s snail venom or snake venom,
they each have components
that can do things
like cause your blood to clot,
what we call “hemotoxic.”
Or they cause neurons in your brains
to not function normally,
what we call “neurotoxic.”
Or they have toxins that will poke holes
into the membranes of your cells,
causing them to rupture
and, basically, explode,
what we call “cytotoxic.”
Cellular explosion, people.
Now, if that is not all powerful
and all present,
nothing is.
Now a little about me,
and why I’m so obsessed with venom.
I grew up in New York City
with forced access
to the Natural History Museum.
I say “forced access,”
because I’m one of five kids,
and my parents used museums
as a form of childcare.
There were two rules:
Don’t lose anybody
and meet Mom and Dad
at the African elephants
at 5:30, when the museum closes.
Those totally unsupervised days
running through the halls of the museum
were full of adventure and exploration.
And that’s how I feel
when I’m studying venom.
It’s a scientific adventure.
We’re boldly exploring this entity
that connects nature and humanity.
Another reason
that I’m obsessed with venom
is because of its duality.
When you inject the components
of a venom arsenal into an organism,
it can kill or it can cure.
At a molecular level,
several things can happen.
You saw one thing, paralysis in the fish.
Now that was happening
because the toxins in the venom
were attacking how the fish’s cells
communicate with each other,
preventing it from swimming away.
Are there other things
that I would like to use venom to attack?
For sure.
And one of those is cancer.
Cancer tumors are cells.
And like all cells,
they communicate with themselves
and their environment around them.
So we would like to find venom components
that are very good at disrupting
how the tumor cells communicate.
Similar to how the venom disrupted
how the fish cells communicated
and the fish couldn’t swim away.
In my lab, we study cancer
as a channelopathy.
What this means is, basically,
we’re looking for venom components
that will target channels
that are overexpressed in tumor cells
versus normal cells.
The cancer that we’re most
focused on right now
is liver cancer.
And that’s because since the 1980s,
the death rate of liver
cancer has doubled,
and it’s an emerging threat in the US.
In a screen in which we had cervical,
neuroblastoma, prostate
and liver cancer cells,
we found a compound from a terebrid snail
that seems to attack liver cancer cells,
and only liver cancer cells,
and none of the others that were tested.
And then, when we took this compound
and we injected it into mouse models
that were expressing liver cancer cells,
it significantly inhibited
the growth of the tumors.
We’re not quite sure how this works yet,
we’re still investigating the mechanism
and how we can make
this compound more effective,
so you can’t rush out to the pharmacy
and order up a killer snail
liver-cancer therapy treatment.
Not yet.
Basically, what we think is happening
is that the compound is blocking
a specific channel,
prohibiting the transmission
of a specific chemical
that leads to downstream signaling
that enables the tumor to multiply
and draw blood to itself.
What we’re doing in studying
the components of venom
to find treatments for human
diseases and disorders,
is not new,
it’s what we call natural
products drug discovery,
and it’s been happening for centuries,
and in cultures all over the world.
Venoms are not only giving us
cool new compounds,
but they’re also giving us
new ways of thinking
about how we treat
human diseases and disorders.
And I’ll give you three examples.
The first is from killer
snails, of course.
And so the first drug from these snails
that is on the market
is called ziconotide, or Prialt,
and it’s used to treat chronic pain
in HIV and cancer patients.
Prialt is a nonaddictive pain therapy.
Three magic words when you think
about how we’re treating pain currently.
We’re using things that have
a huge cost of addiction.
So think of morphine
or think of any of your favorite
opioid out there.
What the snails have done
is they’ve shown us a way to treat pain
without the addiction,
which is huge.
The next example comes
from the Brazilian pit viper.
From these snakes, we’ve derived
a compound called captopril.
Captopril is used to treat
high blood pressure,
and captopril is a breakthrough drug.
But not only in and of itself,
but because it advanced
a whole class of drugs,
what we know as ACE inhibitors,
which are the most commonly [prescribed]
for treating hypertension
and heart failure.
The last example is from the Gila monster.
And this is a really exciting example
of understanding the ecology
of these organisms,
and pairing it with efficient
drug discovery.
And Gila monsters are binge eaters.
So when they bite into a large meal,
they release things in their venom
that lower blood sugar.
So what’s the drug that you think
we found from the Gila monster?
A compound that is used to lower
the blood sugar in diabetic patients.
Now these are three marvelous examples,
but we’ve just scratched the surface.
There’s so much more venom
out there for us to study.
In fact, we think that 15 percent
of all the animals on the planet
are venomous.
And I think this is a low estimate,
given the fact that we haven’t surveyed
all the animals on the planet.
But nature seems to have found
something that she likes,
and she’s repeated it
over and over and over again,
leading to the vast array of animals
that we see around us
and all throughout the tree of life.
So whether we’re talking
about my fave, killer snails,
or jellyfish,
or the larvae of butterflies and moths,
or platypus or slow lorises,
whether by sea, land or air,
you’re sure to encounter
a venomous creature.
Remember when I told you
that venom can be both
a superhero and a supervillain,
and you doubted me?
Mhm.
We’re in a race to harness
all of this venom goodness
before we lose the vast majority
of animals on our planet.
It’s a holistic process.
You can’t have the therapeutic treatments
without having the animals.
And you can’t have the animals
without having their ecosystems.
So for me and the snails,
what it means is
we have to save the oceans.
And because venomous animals
are found everywhere,
we basically have to save the planet.
So do it for the venomous animals,
if you don’t want to do it for yourself.
And who knows,
some day, snail venom
might just save your life.
Thank you.