Hamilton's Pharmacopeia (2011) s01e05 Episode Script

1
Morris:
Land counts for little more
than a quarter
of the earth's surface.
The rest is covered with
326 quintillion liters of water
that the majority of the world's
living organisms call home.
The world's oceans
served as a vessel
for the chemical reactions
that produced life
and neurotransmission,
so it should come as no surprise
that it also contains
an array of compounds
that alter consciousness.
I've been fascinated
by psychoactive drugs
my whole life.
I love to study their chemistry
and impact on society,
and my work has allowed me
to investigate
extraordinary substances
around the world.
Yet, there are still mysterious
that remain.
Its origins
may lay in antiquity,
and the effects are still
being encountered today.
Cultures all over the world
have described reef fish
that produce a drug-like effect
when consumed.
This is the story
of the dreamfish.
I'm off the coast
of Miami, Florida,
with a marine biologist
named Colin Foord.
And we're hunting for
the most dangerous of game --
the sponge.
The sponge in question
is smenospongia aurea,
a golden member
of the class desmospongia
and host to a fascinating
compound called fibromo dmt,
the only known psychedelic
to have been isolated from
the ocean and only the ocean.
The sponges
are sedentary organisms
that obtain their food
by a filtration
of the surrounding seawater.
Even a small sponge can
circulate millions of gallons
in the course of its life.
Let's see what we got.
This is amazing.
It's like ink.
Ink purple.
In 2013, I received a letter
from a Sudanese chemist
who called himself Dr. Oscula.
His letter described
a series of self experiments
with smoked fibromo dmt,
the same drug that was first
detected in smenospongia.
And the report served to prove
an important point --
marine organisms are capable
of producing compounds
that alter human consciousness.
It's so interesting
because containing mushrooms
when they're damp, shells are
this color change, yeah.
They look exactly the same.
We took the sponge back
to Coral Morphologic,
a multi-disciplinary lab
where Colin has devoted his life
to the cultivation
of marine organisms.
One of the things that Dr.
Oscula said in his experiences,
that there was an antianxiety
component to the fibromo dmt
and also a sort of a serene,
underwater, like, vibe to it.
Morris: He's the only person
I'm aware of
that has done this sort of
experiment, and so --
He either needs to do more
experimentation himself,
or needs to provide, uh, samples
to other people
to be able to categorize what
this experience is all about.
I also hope that
this doesn't result in
a lot of people attempting
to get high off of this sponge.
Right. This sponge
is not something
that you can just go and eat
and expect to get high from.
You're not gonna trip.
If anything, you'll probably
end up in the hospital or die.
We're marveling at it as,
you know,
a little organic chemistry
powerhouse
that is producing
a unique compound
that hasn't really been found
elsewhere in nature.
While smenospongia
brings to light
the reality
of marine psychedelics,
there are also reported cases
around the world
of fish causing
vivid hallucinations.
I met with my friend
Jason Wallach
to discuss how we might detect
a marine psychedelic.
Why do you think it is
that psychoactive animals,
in general,
are less researched?
It's a good question.
I mean, I don't know.
It could be a matter
of the complexity
of extracting the chemicals
from the biological matrixes.
And have you
followed this phenomenon,
this hallucinogenic
fish poisoning?
The fact that there are
so many instances
and reports of it occurring
makes me think
there probably is
a real pharmacological
phenomenon going on.
Now, I don't know that that's
responsible for all cases.
I wouldn't be surprised
if there is a chemical
that is contributing to
these altered experiences
that people have.
Hallucinogenic fish poisoning,
also called
ichthyoallyeinotoxism,
has been associated
with the consumption
of at least 16 different species
of herbivorous reef fish.
Those who eat the fish
reported transient intoxication,
vivid dreams, or nightmares,
and in some instances,
open-eyed,
visual hallucinations.
All of the species of fish
that I've seen listed
as potentially, you know,
psychedelic or the dreamfish,
most of them seem like
they're herbivores
in oceanic island areas.
I suspect that it probably has
to do with their dinoflagellates
or -- or -- or algae that --
that certain fish consume.
All attempts to identify the
causal agent in the poisonings
have failed.
To study the effect,
I felt it necessary
to travel to the Indian Ocean,
where most of the implicated
species can be found.
I began my journey
in Madagascar.
[ Speaking indistinctly ]
Here I've got
a species of millipede
that the lemurs in Madagascar
seem to love.
Come on.
Spray juices on my face.
I fed one of the black lemurs
a black millipede,
and he immediately started
shredding it to pieces
with his teeth
and rubbing the juice
from the inside of the millipede
all over his fur
while salivating profusely.
If I didn't know better,
I might think
that the lemur was intoxicated
in some way.
Now it's just staring down at me
and salivating.
I'm on the northern coast
of Madagascar,
hoping to investigate
hallucinogenic fish poisoning.
So, I'm gonna collect
fish samples,
analyze them chemically.
Nobody knows what chemical
is responsible for the effect,
and it remains completely
unknown scientifically.
The reefs around Nosy Bay
are home
to many of the reportedly
hallucinogenic species,
yet there hasn't been
a single account published
describing hallucinogenic
poisonings in all of Madagascar.
So, I met with a retired
shark poacher named Goff
who offered to introduce me
to local fishermen.
Have you heard of people
getting drunk
after eating parrotfish
or goatfish?
Parrotfish has tobacco.
As they say,
it has tobacco in his brain
and also on his gills.
Tobacco in his brain,
that's what she says?
Yeah. Yeah, yeah.
[ Speaking native language ]
Surrounding Madagascar, there
are more than 50 small islands
that possess
their own reef habitat,
providing a home for an amazing
array of marine organisms.
Oh, wow. Wow.
That is a very big fish.
[ Indistinct talking ]
Wow.
Who -- who owns
this table of fish?
Will she talk about it?
Okay, well maybe just put it on
the camera and just ask her.
[ Speaking native language ]
There's two different vendors
selling the parrotfish.
Both of them
became really hostile
and wouldn't talk to us
when he asked about it.
So, no one will answer
my questions about this fish.
Have you heard of any local fish
that produce some sort
of intoxication,
either hallucinations
or vivid dreams?
What fish produces the effect?
Grouper?
What is the effects on you?
Nothing with hallucinations
or a feeling of drunkenness?
The man in the fish market
was likely describing
another phenomenon
called ciguatera.
Associated with the consumption
of grouper,
it's a poisoning that causes
crippling neuropathies,
chronic fatigue, and reversal
of hot and cold sensation
that sometimes lasts years.
Ciguatera, and many other forms
of fish poisoning,
have one thing in common.
They depend on a process
called biomagnification.
Certain substances
can accumulate in the tissue
of an organism at successively
higher levels of the food chain.
In some instances,
fish have evolved immunity
and even maintain
a symbiotic relationship
with toxic microorganisms
to harness their poisons
for defense.
Biomagnification
of certain compounds yet unknown
may be responsible for
hallucinogenic fish poisoning.
I traveled with Goff to a small
island surrounded by reefs
that were said to contain
rabbitfish,
parrotfish, and goatfish.
Goff: I hear about people not
feeling well when they eat it.
But I have never seen people
getting killed of it.
Right.
It's poison.
You tongue and your lips
become with numbness.
You feel a little dizzy.
It can give me some,
like, energy,
but it's not the energy
what I want to get.
What type of fish was it?
It's your rabbitfish.
But I don't know the species,
but it's from the rabbitfish.
Huh, rabbitfish, yeah.
Rabbitfish.
Morris:
I awoke on a small island,
a beauty befitting
a beer commercial,
but was quickly reminded
of marine poisons
as a local fisherman
scaled a grouper on the beach.
He just caught this enormous
grouper near the island,
and now they're scaling it.
Grouper is one of the fish
that's most widely implicated
in ciguatera,
and it seems that ciguatera
is certainly an issue
in this region,
but no one is concerned about
this particular grouper,
for reasons
that aren't clear to me.
Ciguatera is a little known
but incredibly dangerous
and communicable poison
caused by eating
some tropical fish.
Ciguatera survives heat
and most cooking practices.
It's tasteless and odorless,
making detection
nearly impossible.
They are among the most potent
poisons known to science.
How long
have you been fishing?
Do you ever find that the fish
in this area is poisonous?
Can you teach me about the way
that you catch fish?
That's mixed
with bananas?
There it is.
That's a way to catch.
It was an impressive haul,
but the trap didn't contain
a single specimen
of ichthyoallyeinotoxic
interest.
So, I rode onward
to another reef.
The tales of poisoned turtles
and shrill cries of the puffer
emphasized the toxicological
complexity of the ocean
and the difficulties
that I've continued to face
in understanding
hallucinogenic fish.
As the sun set,
I began to feel the weight
of the day's confusions
and decided to set out with Goff
for one final dive
on the reef beside our island.
With only a flashlight,
a trident,
and a pack of condoms,
Goff took me
on a midnight expedition.
[ Laughs ]
Staring across the ocean floor,
illuminated only
by a flashlight,
I saw bleached corals,
octopuses, salp chains,
and organisms I couldn't
even begin to identify.
I began to think about
the ecological role
of a marine psychedelic.
Would it be
to simply deter predators?
Or could such a compound
encourage the desire
to protect
the delicate life below?
I would have to impale small
fish with a trident to find out.
Goff succeeded
in locating a rabbitfish,
and we decided to cook it up
along with a parrotfish
from the market.
As the fish were being prepared,
I frantically reviewed
the literature on the ciguatera.
Both fish were known
transvectors of ciguatoxin.
I was curious about experiencing
the hallucinogenic effect
but not years
of crippling fatigue
and reversal
of hot and cold sensation.
Thank you.
Wow.
Oh, it's really
very aromatic,
breathing in
the fish vapor.
I love it.
Here we have
the parrotfish.
Here were have
the rabbitfish.
This we speared
just a couple hours ago.
Yep.
And today,
we're gonna wet our bed.
Wet our bed?
Yeah.
Why are we
going to wet our bed?
Because we're going to
have a parrotfish.
This is a rumored fact
of the parrotfish,
it causes bed-wetting?
Yep.
Okay.
Wow. All right.
Here's the head
of the rabbitfish.
The smell is more --
so fresh.
How do you learn to fish?
I get it from my grandfathers,
my tribe.
What tribe is that?
Vezu tribe.
Vezu?
Yeah.
Us as a People say "vezu"
because they heard the sound
vezu, vezu, vezu,
vezu, and vezu.
Vezu means paddling,
and they give the name
of the people
in the coastline of southwest
as vezu.
And what about the role of fish
in this culture?
It seems like
everywhere I look,
there's people pulling fish
out of the ocean.
People here living
what they can.
And they take whatever they can,
too.
And from my perspective,
I'm trying to understand
chemically and pharmacologically
why it is
that certain fish
seem to have this effect.
But then
when I go underwater
and look at the diversity
of organisms,
it seems like it's almost
a hopeless investigation
because there's so many
different things in the ocean.
There's so many different
bacteria, dinoflagellates,
seagrass, algae.
Might be a fish himself
is producing that one.
I feel like it's making my mouth
slightly numb. Is that normal?
Yeah.
Yeah, it's making my tongue
totally --
it's making my tongue
completely numb.
Oh, yeah, you just enjoy it.
You'll be fine.
For sure.
Outside of an explicable
oral numbness,
the fish were without activity.
Could the local reports have
been nothing more than placebo?
I wanted to continue searching,
so my next stop
would be on an island
where the locals are rumored
not only to know
of psychoactive fish
but to get high on them.
[ Laughs ]
[ Native singing ]
Morris:
After last night's dinner
with Goff,
I wanted to experience
a different species of fish
that has been used
on Reunion island for decades.
The most extensive review
of hallucinogenic fish poisoning
was authored by a naval surgeon
named Bruce Halstead
as part of
his 3,000-page magnum opus
"Poisonous and venomous
marine animals of the world."
The author of this book,
Halstead,
even claimed to have discovered
what chemical is responsible
for hallucinogenic
fish poisoning
but refused to tell the public
because he was afraid that
the Russians would use it
against the United States in
some kind of military capacity.
There's a little bit
of wackiness
surrounding this research,
as well.
[ Native singing ]
Based on ancient pottery from
the Moche civilization in Peru,
anthropologists have argued
that a psychoactive blenny
known today as pez borracho,
or the drunken fish,
may have been used
in sacrificial rituals.
But it wasn't until 1927
that modern reports
of hallucinogenic fish poisoning
began to appear.
They described effects that
ranged from vivid nightmares
and perceived strangulation
to hallucinations
that are actually enjoyable,
which brings me to Reunion.
Regional variation in toxicity
amongst the implicated species
suggests that the toxin
is dietary in origin.
So, I began dissecting
the rabbitfish
and collecting their viscera
for microscopic analysis.
Here we have the liver
and stomach.
Oh, wow, yeah,
that's the stomach.
And you can tell
because of the horrific odor
and also the green contents
which are indicative
of the algae
that the fish consumes.
The rest of the fish's body
I would save
for chemical analysis
in the United States.
Some of the stomach contents
are even beginning to ooze out.
[ Coughs ]
Oh.
Ugh.
Ohh!
It's spilling everywhere.
All right.
Dream-inducing drugs,
also called oneirogens,
are a relatively unstudied
but real phenomenon.
Such effects
are commonly reported
in hallucinogenic
fish poisoning,
leading some fishermen
to call them nightmare fish
or dream fish,
depending on their experience.
I arrived the next morning
in Reunion,
a French territory
that maintains
a very different culture
from that of Madagascar.
With a distinct Creole language,
it's home to a wide variety
of ancient seafaring tribes.
Since 2011, bull sharks
have attacked 19 surfers,
7 of whom died, making the
island infamous internationally.
It was along
Reunion's rocky coastline
that I encountered a fisherman
using algae as a bait
to catch herbivorous reef fish.
Have you ever personally
consumed one of these fish
that produces
hallucinations?
What was it like?
The reef habitats of Reunion can
be best understood from the air,
so I boarded a helicopter
with Jean-Pascal Quod,
a world-renowned
marine biologist
who has studied marine toxins
and their associated
microorganisms for 35 years.
Here we go.
10,000 years old
and young for a reef?
Yes.
In 1998, a belt of coral reefs
surrounding the western coast
of Reunion
was impacted
by a bleaching event.
The coral has struggled
to survive ever since.
The bleaching and death of coral
creates a home
for opportunistic microalgae
that, in turn, provide a home
for toxic dinoflagellates
that produce ciguatoxins.
The combination
of climate change
and chemical contamination
of the ocean
has made these
toxic microorganisms
ever more abundant.
Yeah.
Yes.
There's some basic ambiguity
about whether or not
this is a real thing
or whether it's food poisoning
or placebo effect,
something that people
are imagining.
I'm assuming that it's real.
You don't know
if it's one single thing
that everyone is describing
or dozens of different things
produced by completely different
marine drugs.
It looks like there's so many
things growing on top of
the algae, as well.
Should we look inside
the stomachs of the
fish we collected?
Yes, but after that, we close,
and we go very far away.
The alcohol doesn't reduce
the odor at all?
No.
I was hoping to find fragments
of caulerpa or lyngbya
or maybe even bryopsis.
But instead, I found
unidentifiable muck.
You think it's feeding
on microalgae,
or because it's decomposed
in the digestion?
Yeah.
What about if you go
deep on the bottom?
It's only sand?
Yeah.
Another source, like Lyngbya,
which is host to several
cannabinoid fatty acids,
or red algae,
from the genus laurencia,
which contains sulfurous
polybrominated indoles,
or the tunicate
aplidium conicum,
which produces a
tryptamine-based
histamine antagonist,
or desformylflustrabromine
from the bryozoan flustra
foliacea.
Or even an atypical response
to dinoflagellate-derived
polyether neurotoxins
known and unknown.
It's very complicated.
It is complicated.
The mystery remains.
Morris:
Just when I thought my chances
of experiencing
hallucinogenic fish poisoning,
or ichthyoallyeinotoxism,
or even
were close to nil.
I met with two local fishermen
known as the Creole brothers
who are rumored
to consume black surgeonfish
not just to feed their bellies,
but to feed their minds.
What do you think it is that
gives the fish this activity?
Are other people afraid
to eat this fish?
With my departure back
to the United States imminent,
this dive would be
my last opportunity
to collect samples
of the elusive dreamfish.
This is my first time diving
in water like this,
which is generally off-limits
because of the enormous number
of man-eating sharks.
Oh, wow.
Very brutal.
It's interesting, the way
the blood looks underwater.
It looks green
when they spear the fish.
It's as if
they're hemorrhaging green.
So, do you think
these are the type
that will produce
the drug effect?
The drunk feeling?
Though I requested they separate
the fish by species
and refrain from using spices
that would confound
any observed effect,
the brothers mixed the day's
catch together in a single pot
and set about collecting
curry leaves from their garden.
The Creole brothers said
that they feel it,
but sometimes other people
in their family don't feel it.
Assuming that it's real,
you don't know
if it's one single thing
that everyone's describing
or maybe dozens
of different things
produced by completely different
marine drugs.
We're all going to eat it
together
because they said that
it will make us drunk.
So, that's intentional.
We're taking fish to get high.
Morris: Earlier today,
we went out fishing.
We caught
three different species
that these fishermen claim
produce some kind of
inebriating effect.
They say that
it makes you drunk
or that it increases
the vividness of your dreams.
They just prepared all the fish
together in one pot,
which is right here.
So, I don't know
which species it will be,
if I feel anything,
if it'll be all three together
or one of the three.
It's gonna be hard to know.
This makes things
even more complicated.
How many do you think
I should eat, to have an effect?
Is this enough?
Very good, thank you.
It takes like curry
because it's curried.
Um, other than that,
it has a somewhat flavorless
white fish-type taste.
And my mouth does feel
a tiny, tiny bit numb.
Have you ever had a drunk
feeling from eating this fish?
Why do you eat it
in the family?
Is it as active
psychologically?
Are the dreams good dreams,
or are they nightmares?
Hmm, sleep paralysis.
Is that the brain?
Suck from here?
[ Slurping ]
[ Laughter ]
Sorry. Mm.
Mm.
The other head?
Okay.
Should I just keep eating
fish heads?
Should I have
a fifth fish head?
[ Voices distorting ]
Aah! Jesus Christ.
My whole body went numb,
and I dreamed
that the camera crew
had taken my mattress
and put it out floating
in the ocean
as a prank or something
to get good footage.
And it seemed completely real,
it was so vivid.
And I saw you pointing
to a computer monitor,
but it was like you were trying
intentionally to freak me out,
pointing to a flat-screen TV.
And then it zoomed in on, like,
a security camera in the lobby
into so-- to the back
of an old man's head.
And then I started screaming,
and I had sleep paralysis
and woke up.
It was really unpleasant.
I dreamt -- I had a totally
non-frightening dream
about riding a bike
and talking with you and Jean
about buying books on Amazon.
[ Laughs ]
[ Man speaks indistinctly ]
And whether it was
a better use of money
to see movies in theaters
or buy books on Amazon.
[ Laughs ]
Morris:
When I awoke the next morning,
the numbness was gone.
And besides feeling
like somehow, in my sleep,
I had traversed oceans
and continents,
the effect of the dreamfish,
whatever it may have been,
seemed to have worn off.
So, Hamilton, what about
yesterday experience, uh,
with the, uh, fish?
I ate the fish, and then they
insisted that I eat the heads.
So I ate five fish heads.
Okay.
And they insisted that
I eat the brains.
And so I started
eating the brains,
and then they asked me to slurp
the liquid out of the head,
to sort of suck
on the skull
until all of the liquid
had exited.
And I drank that liquid.
It did not taste good.
Then I lay down and immediately
started dreaming
and then woke up.
Then I went back to the hotel,
fell asleep again,
had extremely
intense dreams
where I was
telepathically communicating
with one of the cameramen.
Okay.
Then had
a sleep paralysis episode
where I become terrified and
tried to wake up but couldn't
and tried to scream
but couldn't.
And woke up sort of
silently attempting to scream.
So, that was
probably negative.
But even though I did wake up
screaming twice,
it wasn't that bad.
I would say that, overall,
it was pretty neutral.
The time had come for me
to leave Reunion and Madagascar
behind
and return to the United States.
The fieldwork was over.
Waiting for me
were dried rabbitfish
that I had collected
and sent back for my research.
There I would begin
the analysis.
The dried fish specimen that
I collected in Madagascar.
When I was talking with
J.P. Quod about this research,
he suggested
dividing each fish in half
and eating one half
and then saving the other half
for analysis.
That way, if there was
a drug effect from the fish,
I'd have a reference
from that same fish.
The problem is that, even things
like ciguatoxin and maitotoxin
are hard to find
in the first place.
Even if we knew
what we were looking for,
I'm not sure that we'd be able
to find it in this fish.
18 grams of dried rabbitfish
was finely chopped,
soaked in 300 milliliters
of ethanol,
and sonnicated at 40 kilohertz
for an hour.
This extraction
was repeated twice.
The pulled ethanol was filtered,
concentrated,
and loaded onto
a silica gel flash column
with a mobile phase of hexanes
ethyl acetate in a 3-to-1 ratio,
followed by increasing
concentrations of ethyl acetate
and finally ethanol.
72 fractions were collected
and analyzed by an ASAP MS.
This is what the crude
fish extract looks like.
We also did chromatography.
We looked at
some of the pure fractions,
but ultimately,
this is representative
of the different compounds that
were detectable in the fish.
The base peak is 257.12.
Neither of us can figure out
what exactly that is.
None of these things
are jumping out
as obvious candidates
for something
that could explain
ichthyoallyeinotoxism
or hallucinogenic
fish poisoning.
Certainly no fibromo dmt,
no brominated compounds
of any kind.
No detectable ciguatoxin
or maitotoxin.
Maybe it's purely psychological.
Maybe it's a placebo effect.
Something mass spec
cannot detect.
It's not a very satisfying
answer, unfortunately.
Wallach: The history
of medicinal chemistry,
organic chemistry, are filled
with alkaloid extractions
from plants.
Uh, in some cases,
other living organisms.
It was something,
in this situation,
where we don't know
what we're looking for.
We don't have
an animal model
for testing
the psychoactive effects.
It's very difficult
to fractionate it.
I mean, you end up
with 100 fractions,
and each of those fractions
has multiple chemicals in it.
So you could separate it,
reiterate 1,000 times,
and end up
with 1,000 different chemicals
and still not have a model
to test which contains
the psychoactive component.
The fish,
there were multiple species
that were implicated
in this effect,
so it becomes very difficult
to know where to begin.
Right, yeah.
I mean, is it even one chemical?
It could be multiple components
that are contributing
to the effects in different
geographical regions.
Even different seasons.
I think
it's a very difficult issue.
It's a fascinating one,
but I think it's something
that would require
someone that is willing
to dedicate a career
to solving.
In a world
where the majority of organisms
possess neither the ability
to hear nor vocalize,
the common language is chemical.
These organic chemists
of the deep
have created
an ever-evolving pharmacopeia
with drugs and poisons emerging
and disappearing
as the chemistry of the ocean
is transformed
by the impact
of human civilization.
Somewhere between science
and cryptotoxicology,
the identity of
the hallucinogenic fish poison
has eluded researchers since the
phenomenon was first reported,
but that doesn't mean
we should stop looking.