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The use of poisons in war, specifically
poison gas,
started in the First World War.
But one of the most potent poison gases,
nerve gases, ever discovered is the
compound called Sarin.
And this was developed by the Germans in
the 1930s and taken over by the German
military.
And in the World War Two, the Germans
stockpiled a lot of Sarin
but it was never used, and most of it was
discovered by the Russians as they pushed
through into Germany.
All sorts of countries have made and have
stockpiled Sarin
and most, quite recently, we've seen the
United States going to the verge
of military action against Syria because
of the use of Sarin in the Syrian Civil
War.
One terrible use of Sarin was back in
1988,
when the Saddam Hussein's military in Iraq
used it against
villagers up in Kurdistan, in the north of
the country.
Sarin is a very, very powerful nerve
agent.
It gets into the body,
it stops the nervous system working,
and even with very low doses, causes
death.
It's not just governments that have made
Sarin.
This cult, this Japanese cult called Aum
Shinrikyo, also had a go at making Sarin.
And they released some in a town called
Matsumoto
in June of 1994, killing seven people.
The following year, they carried out the
well-known Tokyo subway
attack, where they released their home-made
Sarin in the Tokyo subway.
They killed 12 people.
A thousand people, at least, went to
hospital, and even today,
there are still people suffering the ill
effects of that attack.
Fortunately, the Aum Shinrikyo chemists
weren't very good at their job.
The Sarin they produced wasn't very pure,
and it smelled very badly.
If they'd made pure Sarin, then the death
toll would have been much, much higher.
Well, how do these nerve agents work?
They work by interfering with the
biochemical mechanism in
which nerve impulses travel from the brain
to the muscles.
So this is a nerve cell, and it does look
like a piece of wire,
and in some ways it acts like a piece of
wire in transmitting the message.
So, how does a nerve cell actually work in
chemical terms?
Well, let's consider a nerve cell in it's
resting state,
where nothing is going on.
Here's the nerve cell,
before it is the previous nerve cell,
in front of it is another nerve cell.
And it's this line of nerve cells which
will
ultimately carry the impulse from the
brain to the muscle.
Well, in the resting state,
there is potassium ions inside the cell,
there's sodium ions outside the cell, and
the cell has a slight negative voltage.
At the business end of the cell, there is
a little molecule sitting there.
This is called the neurotransmitter, and
the job of the neurotransmitter is
to jump across the synapse to trigger the
next nerve cell in the line.
Okay, the signal comes down the line, the
neuron
becomes excited, and passageways in the
cell wall open up.
And these passageways are sodium channels,
they will allow sodium to flow into the
cell.
So sodium flows from outside the cell into
the cell, which means that the voltage
becomes positive.
So the neuron is excited,
it's now at plus 30 millivolts, and the
neurotransmitter is released.
Now this neurotransmitter is a little
molecule called acetylcholine.
It's released, it crosses the synapse, and
when it gets to the nerve cell on
the other side it then excites that one,
and the message continues down the line.
So the nerve cell that we're looking at
now has to get back to its original
state.
Passageways in the cell wall open, these
are potassium channels, and potassium is
released.
The final thing is that iron pumps
redistribute the sodium and the
potassium, so the potassium goes back in
the cell, the sodium comes out,
and we're back where we started, we're
back at the original state.
Now, the neurotransmitter has done it's
job.
So at some point it either has to go back
to where it started, or it has to be
removed.
And it's removed by being destroyed
by a particular enzyme called
acetylcholinesterase.
And this whole process takes two
milliseconds, very
remarkable piece of chemistry. But
remarkable piece of chemistry,
what happens when we interfere with it?
Sarin interferes at the neurotransmitter
stage.
Suppose we have excess of the
neurotransmitter present.
What will happen?
Well, it means we get continued nerve
stimulation.
Even though there is no signal coming down
from
the line from the brain, the nerve is
still stimulated,
and that means that the muscles at the end
of the nerve are still activating.
This leads to twitching.
It leads to convulsions, it leads to
paralysis and death.
It often starts with blindness due to the
effect
on the eye muscles and the eye nerves.
Now, under what circumstances would we
have excess of the neurotransmitter
present?
Well, the concentration of the
neurotransmitter is regulated by this
enzyme
called acetylcholinsterase, which
converts
the acetylcholine into inactive choline.
What Sarin does is block the action of
that enzyme
so that the excess acetylcholine cannot
be destroyed, and therefore will be present in
excess.
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Well, I don't know if you've seen this
movie, it's called The Rock, it
was made a few years ago, and it stars as
the heroes, Sean Connery
and Nicholas Cage, with Ed Harris as the
villain.
Well, in this movie, some renegade US
soldiers
steal some Sarin containing chemical
weapons and take over
the island of Alcatraz in San Francisco
bay,
and threaten to fire these weapons at San
Francisco.
So Nicolas Cage and Sean Connery are
sent into Alcatraz to defeat this
dastardly scheme.
In a scene towards the end of the movie,
Nicolas Cage
is exposed to Sarin when one of these
things go off,
and very dramatically, he pulls out this
syringe he's been given earlier on
and he stabs himself in the chest with
this syringe.
And then everything's fine, and the bad
guys are dealt with,
and Nicolas Cage gets the girl,
and there's a happy ending.
Now what was in the syringe?
The answer is
a naturally occurring chemical called
atropine,
and atropine is the antidote to Sarin.
The reason it's the antidote to Sarin is
because it has the opposite effect.
Whereas Sarin inhibits the action of
acetylcholinesterase, the enzyme,
atropine inhibits the action of acetylcholine.
So if you
have excess acetylcholine present,
atropine will prevent it from acting.
So the atropine does the opposite to
the Sarin.
So, provided the doses are about balanced,
then it's going to work as an antidote.
On the other hand, if you take atropine
just as
atropine and not as an antidote, then it
will be toxic
because it's going to inhibit this action
of your neurotransmitter.
And as you can see there, there is
an LD50 for atropine in rats by oral
administration.
Now atropine, as I said, is a naturally
occurring compound,
and it comes from the plant Atropa
belladonna.
So it gets its name from the Atropa
part, but what about the belladonna?
Well, belladonna is Italian for beautiful
lady.
And one of the effects of atropine is
that if
atropine is placed in the eye, then the
pupil dilates.
So the pupil becomes bigger, and many
people
consider this to be beautiful, hence,
belladonna, beautiful lady.
And in fact, one of the uses of atropine
is in optometry,
because if you put it in someone's eye,
and you dilate the pupil
to make it bigger, then it's easier for
the ophthalmologist to see inside.
Provided it's only on the surface
of your eye,
it's not going to do you any harm at all.
But, of course, if it's ingested then as
we know, it's toxic.
I mentioned at the beginning of this
lecture
that one of the reasons that poisoning is
less common nowadays than in the old
days is because it's much more difficult
to
get hold of these very, very poisonous
substances.
However, one group of people who can get
hold of these substances relatively
easily are chemistry professors.
And this case here involves a professor
of biochemistry, Paul
Agutter, who used to be at Napier
University in Edinburgh, Scotland.
And he was convicted of poisoning his wife
with atropine, which he obtained
ostensibly for research purposes.
So, how did Agutter do it?
Well, he put atropine in his wife's gin &
tonic.
Now, if a wife is murdered, then of
course one
of the first suspects is going to be the
husband.
And Agutter knew this
so he laid a false trail to try and
mislead any investigators.
He went to a local supermarket and took
some of the bottles of
tonic water and spiked them with atropine,
and then returned them to the supermarket.
His idea was, by having random people
around the town having mild atropine
poisoning,
people would think this is some kind of
serial killer, or
maybe someone with a grudge against the
supermarket, or the drink manufacturer,
rather than a husband trying to get rid of
his wife.
Unfortunately for him, his scheme
unravelled,
and that is because the amount of atropine
he put in the tonic bottles
was less than the amount of atropine that
he put in his wife's drink.
These things, of course, are very easy to
measure using a technique such as HPLC.
So it was very clear to the police that
it was actually
a husband-wife case rather than a mass
poisoning.
Well fortunately, his wife got medical
treatment,
she survived, and Agutter was convicted
only of
attempted murder, and he served seven
years in prison.
Interestingly, after his release from
prison, he started to work for the
University of Manchester, and they asked
him to teach a course on medical ethics.
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