[MUSIC]
Well, we've been talking about poisons,
but we haven't actually defined a poison.
So let's give a definition of a poison.
We can say a poison is "any substance
which, if taken
into or formed in the body, destroys life
or impairs health."
So that's quite a straightforward
definition of a poison.
Now we consider that the first
toxicologist, the founder of
toxicologists, was this man here,
Philippus Aureolus Theophrastus
von Hohenheim, who lived in the first half
of the sixteenth century.
Now that's quite a mouthful of a name,
so typically he went by the pseudonym,
Paracelsus.
And Paracelsus was the first person
to really think scientifically about
poisoning.
Paracelsus is also a medicinal chemist
and he realized that many substances that
are poisonous can also be medicines.
In particular, he was very fond of using
mercury, and he made a very, very good
point.
He said that "all substances are poisons,
there is none
which is not a poison". But he pointed out,
that it is "the
right dose that differentiates a poison
from a remedy",
and he was absolutely right.
All substances are poisons, even a
substance as common as water.
Well, poisoning by water is not common,
but every so often there is a case.
The thing is that, to be poisoned by
water, you need to drink a lot.
About seven litres is probably the lethal
dose for water.
So a few years ago, a California radio
station, KDND in Sacramento, decided to
have a competition.
And the title of this competition was "Hold
your Wee for a Wii"
and the idea was to see how much
water people could drink without going to
the bathroom,
and whoever could drink the most would win
one of these game stations.
Well this unfortunate lady here, Jennifer
Strange, really wanted to
win one of these things to give to her
children.
So she took part in this contest
and she probably drink, drank about 7.5
litres of water.
And then after the contest, she drove
home.
She apparently didn't feel well, so she
went
to bed, and later, she was found dead.
Well of course, this was the United
States, so quite rightly, her family sued
the radio station and they were awarded compensation
to the tune of $16 million
U.S. dollars.
What is interesting is that Jennifer
Strange
didn't win the contest, she came second.
The winner of the contest was a lady
called Lucy Davidson, and she survived.
And she said this,
"I didn't know what was wrong with me, I
just
knew I had never felt so sick in my life."
So there you go, all substances are
poisonous, including water.
Well, here's another example.
This is a wild plant that grows in Europe,
it grows in the
woods, people grow it in their gardens,
it's very common, it looks very nice.
It's called the foxglove, and it's
poisonous.
It contains a chemical called digitalin,
which is a potent heart stimulant.
So, if you eat too much of foxglove,
your heart will be over-stimulated, and
you'll die.
But this same chemical, digitalin, which
is contained
in the foxglove, is in clinical use.
If someone's heart is failing, they will
be given a controlled dose of digitalin
and their heart will beat properly and
their life can be saved.
So just as Paracelsus said, the difference
is the dose.
So nowadays, we talk about dose-response
curves.
So if we have a particular substance in a
low dose, there's
no response, the body can handle it,
there's no effect.
If the doses is increased, then we start
to get mild toxicity, some illness.
Further increase, we will get severe
toxicity,
where the person is very ill and
suffering.
Then above a certain dose, of course, this
will lead to death.
So this is a typical kind of dose response
curve.
Of course the steepness of the curve, how
soon it leads to
death, is going to be very, very,
variable depending on the chemical.
You'd need seven litres of water at
least, in order to
kill somebody, but for some chemicals, you
may only need milligram amounts.
So, how do we measure toxicity?
The number we use is called the LD50.
This is the lethal dose for 50 percent.
It is the amount of chemical that has to
be administered
to kill half the population of a given
set of test animals.
So, suppose we have a group of mice, and
we
dose them with this poison until half of
them drop dead,
and then we've found the LD50.
Now, how accurate is LD50?
Well, the answer is, not very.
For a start, LD50s will vary according to
how you administer the poison.
Orally administered poison versus an
injection straight
into the bloodstream is going to be
different.
Further, the LD50 is going to depend on the
species you use for the test.
So typically, this is done on animals like
mice or rats,
and then we take those LD50 values for
those creatures
and we assume that the LD50 for human
beings is going to be something like that.
But it's not necessarily so.
Take the case of chocolate.
Most people are well aware that chocolate
is poisonous to dogs.
You shouldn't give chocolate to your pet
dog because it's going to make him ill.
And yet, consider human beings.
I know some human beings for
whom chocolate is actually an essential
nutrient.
So quoted LD50 values are not
scientifically
firm and precise, they are a guideline.
But it's the best we've got.
So here are some typical LD50s for a range
of
poisons going from sodium cyanide right
through to the botulism toxin.
And the units in which LD50s are quoted
are typically in milligrams
per kilograms, or here, micrograms per
kilograms,
and that is because we must always measure
the dose per unit body weight.
Obviously, if you're testing it in mice,
mice
are very small, much smaller than a human
being.
So you need a tinier dose for a mouse than
for a human, just because of the
difference in size.
So LD50s are always quoted per unit body
weight.
So size affects how much poison is lethal.
Age also has an effect.
Small children are easier to poison than
adults,
simply because their metabolism is not
fully developed.
Older people are also easier to poison,
because metabolism changes with age.
The state of someone's health also has an
effect, in particular, the condition of
someone's liver.
Someone with liver disease is going to be
more
susceptible, and we'll see why that is in
a moment.
History is important, and this is because
the body can develop tolerance to certain
poisons,
and we'll see an example of this later
when we talk about arsenic.
But another example would be, for
instance, a heroin addict.
Suppose you have someone who is injecting
heroin habitually.
In order to get the same high, they
typically have to keep increasing the dose
they inject.
Now heroin is very, very toxic
but as they gradually build up the dose
they're
taking, their body builds up a tolerance
of heroin.
So they can inject a dose of the stuff
that would kill a normal person.
Now suppose that heroin addict is then
arrested and goes to prison,
spends some time in prison where he
doesn't have any access to heroin,
and then he comes out of prison and the
first
thing he does is give himself a dose of
heroin.
Now while he's not been exposed to the
stuff
in prison, he could well have lost his
tolerance.
So when he comes out, gives himself his
normal dose,
it kills him because his tolerance is
gone.
And then, the human body is a very, very
complex thing,
and we sometimes see what are called
paradoxical reactions.
And this is where the body reacts to a
substance which
is actually not considered poisonous, but
it leads to their death.
An example is the anti-malarial medicine
Lariam.
If you go to a part of the world
where malaria is endemic, then typically
your doctor will advise
you to take a substance such as Lariam,
just in
case you get bitten by one of the
parasite-carrying mosquitoes.
But Lariam is well-known that it can cause
side effects.
In some people there are no side effects,
I never got any side effects when I took
Lariam.
But it's well known that some people go
into depression caused by Lariam,
and sometimes that depression
can be extremely bad.
So here's a case, a student called Vanessa
Brunt, very, very smart, had a
place in a good university all lined up,
but she took a year off
and she went to South China to teach
English.
And she went to a part of South China
where malaria is endemic.
And so, following advice, she took Lariam
and it caused an extreme depression,
which led to her suicide.
So if you're travelling to one of these
places, then you have to balance out the
risks.
What's the risk of getting malaria versus
the risk of a paradoxical reaction?
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