Poison Pain, Pus and Poison: The Search for Modern Medicines

This is Walton Hall in Yorkshire.

In 1835, it was home to a wealthy and somewhat eccentric gentleman.

They said he could be seen regularly walking the grounds bare-footed,

and in the company of an ageing donkey.

Now they must have been a pretty shabby pair

but, between them, they took part in one of the more extraordinary

experiments of the 19th century.

An experiment that would lead to significant breakthroughs

in medicine and in surgery,

and would transform our understanding of poisons.

Come on then.

Pain, Pus And Poison has charted the many colourful characters

who, over the past 200 years, created the medicines

which protect us from pain, infectious disease and even death.

Through their heroic efforts,

chemicals almost magical in their effects were discovered,

scrutinised, and finally exploited.

In this programme, I'll reveal the remarkable science behind perhaps

the most unexpected source of many modern medicines.

Poisons.

Poisons that include the planet's most deadly substances.

A couple of kilos would kill every human on the planet.

From the natural world to the man-made,

it's a tale of greed, tragedy, hope and chance.

What started out as a science expedition looking at bugs

turns into a cancer therapy.

To me, I think that's one of the wonders of science.

So just how far can we go into unlocking the benefits of poisons?

All medicines are poisons and all poisons should be considered

as potential medicines.

This is the story of how we have turned killers

into cures.

Poisons have, throughout history, been used to take life,

whether by suicide, assassination or murder.

And yet, until the 19th century,

surprisingly little was known about how they actually work.

Someone who helped change that was Charles Waterton,

the colourful squire of Walton Hall.

He was considered very eccentric.

He used to sometimes hide under tables

and bite people's legs at the dinner table.

He was double-jointed.

He could scratch behind his ear with his big toe.

He was an avid tree-climber.

He climbed trees into his 80s. That's quite strange.

As well as being an eccentric,

Waterton was also a man with a passion for knowledge.

He travelled the globe, collecting the exotic and

the unusual, not always simply for scientific study.

He created a taxidermy piece after a customs officer had upset him by

charging extra duty on the specimens he'd brought back from Guyana.

He changed the rear end, the arse of a Howler Monkey,

to look like this customs officer's face,

which is possibly the perfect insult.

Waterton spent nearly 20 years living in the Amazonian rainforest,

where he befriended one of the Amerindian tribes,

called the Macushi.

Now what Waterton was really interested in

was a closely guarded secret -

a poison that could kill almost any animal,

and which occasionally they used to kill each other.

He managed to get the recipe from the Indians.

It's got some really interesting ingredients.

We've got the fangs of the Labari Snake,

and there's also apparently some Black Ants you pound in,

which are so venomous their sting alone produces a fever.

But it's actually not those things.

The key ingredient is a vine which grows in these wilds,

which is called Wourali.

It is from this that the poison takes its name,

and this is the principal ingredient.

This vine was later identified as strychnos toxifera.

And the poison from it is known today as Curare.

Now, these are real samples that Waterton brought back

200 years ago -

a bowl in which you'd sort of mix up the ingredients,

and these are the poison darts.

In fact, the poison is the black stuff on the end.

That is Curare. And although it is 200 years old,

it's still active so I'm not going to touch it.

Now, Waterton himself brought it back because Europeans

were absolutely fascinated by Curare and no-one else had

succeeded in getting the really good stuff in quantities.

Certainly not enough to do proper experiments with.

Back home, Waterton was approached by leading vet

Professor William Sewell,

and eminent surgeon Sir Benjamin Brodie,

who wanted to find out exactly how Curare killed its victims.

Brodie had already tested the poison on small animals,

but now wanted to experiment on something larger.

So they used a donkey.

They injected the unfortunate donkey with enough Curare to kill it.

Then when it collapsed and stopped breathing,

they quickly performed an emergency tracheotomy.

What you do is you get a knife

and you slit your way into the windpipe here,

and then what they did is they inserted a pair of bellows into

the windpipe and pumped away.

And they really had very little idea of what they were doing.

They didn't know how long they would have to do it for.

After about two hours,

the donkey sort of recovered enough

to look up and sort of stare at them.

So they stopped, and the donkey then collapsed.

So back to the bellows again.

They kept this up in total for about four hours.

Until finally, as Waterton wrote in his journal,

the pumping had saved her from her final disillusion.

She rose, she walked about without obvious agitation or pain.

Yes.

Waterton, Sewell, Brodie and, of course, the donkey,

had demonstrated something remarkable.

A discovery that would have an unexpected

and far-reaching impact.

They had shown that curare acts on specific muscles,

including those that enable you to move and breathe.

Whereas other muscles, including, crucially, the heart,

were completely unaffected.

As long as you can keep the patient breathing,

he, she or it, should survive.

The key aspects of curare is that it's a muscle relaxant.

All your voluntary muscles will stop working,

including the respiratory muscles.

The three scientists had shown it's possible to keep a patient alive

while their body is rendered immobile, relaxed by curare.

Now, in the early 1800s,

this discovery had no obvious application.

But 100 years later, it would transform surgery.

In the mid 20th century, one of my favourite self-experimenters,

Dr Fred Prescott,

deliberately injected himself with a pure form of curare

to demonstrate that it is safe to use

as a form of muscle relaxant in surgery.

In fact, since the 1950s, most people who've had major surgery

will have benefited from curare or one of its modern equivalents.

And the donkey, she was retired to Walton Hall.

Charles Waterton wrote in his diaries,

"She shall be sheltered from the wintry storm.

"And in summer, she shall have the finest pasture.

"She will end her days in peace."

In fact, she did live another 25 years.

And when she finally died in 1839,

she got her own obituary in the local paper,

detailing her contribution to medical science.

In Victorian Britain, life was harsh and often cut short.

Life insurance suddenly became a boom industry.

This led to a surge in financially-motivated murders.

Many by poison.

These poisonings would, in turn, have unexpected consequences

for pharmacy and forensic science.

One of the most high-profile Victorian cases

was a woman called Mary Ann Cotton.

She was married four times.

Three of her husbands, heavily insured, all died.

The one who survived seems to have done so

because he refused to take out insurance, so she left him.

In all, 10 of her children died

of what appeared to be gastric-related illnesses.

Tragic and terribly sad,

but fortunately, most of them were insured.

Her mother, her sister-in-law and her lover

also died and in each case, she benefited.

By 1872, the unfortunate Mary Ann

had lost an astonishing 16 close friends

or family members.

But there was one left.

Her seven-year-old stepson, Charles Cotton.

Now, she tried to give him away to the local workhouse,

but they wouldn't have him without her.

Young Charles soon died.

The manager of the workhouse, however, got suspicious

when he heard about the death of the child and he contacted the police.

They investigated and exhumed the body of young Charles.

They suspected foul play.

And, not surprisingly, wondered if Mary Ann had poisoned him.

BELLS PEAL

They thought they knew how she'd done it.

With arsenic.

Arsenic was an excellent way to kill somebody.

It's known as a cumulative poison,

which means that you don't excrete the dose.

So in other words, the more you take,

it builds up more and more in the body.

And it was very easy to administer in food.

So it just looked like somebody was dying of natural causes.

The trial of Mary Ann Cotton would hinge on whether

they could find traces of arsenic in the body of Charles Cotton.

Now, forensic science was still in its infancy,

but they did have a good test for arsenic.

The reason for that is,

there was an awful lot of arsenic-poisoning around.

This test is called the Reinsch test.

And it was the one used to discover

whether Mary Ann had poisoned little Charles.

A sample from the boy's stomach and intestines

was heated with acid and copper.

If arsenic was present, the copper would turn dark grey.

And when placed on paper soaked in mercury bromide,

produce a tell-tale yellowy-brown stain.

And when they did this test on the body of poor little Charles,

they discovered that he had indeed died of a lethal dose of arsenic.

His stepmother Mary Ann

was convicted of his murder on the basis of this

and she was hanged in Durham jail in March, 1873.

She was never taken to trial for the mysterious deaths

of her mother, three husbands, two friends

and 10 other children.

Throughout the 19th century, tales of sinister poisoners

and unfortunate accidents filled the newspapers.

And it was because arsenic was such a silent and prolific killer

that some of the earliest techniques in forensic science were developed.

But arsenic was about to do more than that.

It was about to shape the development

of the modern drug industry.

Now, I'm feeling quite nervous

because this stuff is really, really nasty.

It actually is a mineral,

and even a tiny, tiny amount,

less than a hundredth of an ounce, would kill you.

As a poison, it is almost unrivalled

because it's completely tasteless, dissolves in hot water

and it takes so little to kill.

I'm going to put that back in there and then...

Ooo! Go and wash my hands.

Arsenic trioxide was marketed as a rat poison.

It was cheap and easily available.

Children would blithely collect it from the shops,

along with tea, sugar and dried fruits.

A fact satirised in this Punch cartoon from 1849.

And yet there was clear evidence of it being used to murder people.

So pressure was growing to bring this deadly poison

under some sort of control.

The Pharmaceutical Society,

along with what became the British Medical Association,

got together in 1849, went to Parliament

and lobbied for a new law to actually stop these poisonings.

As consequence, a new act was passed which was the 1851 Arsenic Act,

which greatly restricted the sales of arsenic.

The new act said that if you were selling arsenic over the counter,

then you had to keep a record.

You also had to know the person you were selling it to.

And finally, in future, all arsenic

would have to be coloured with soot or indigo.

So presumably, if your husband or wife was trying to poison you,

then you had a better chance of detecting it.

It had even been proposed

that women should be banned from buying arsenic.

But that measure didn't make it onto the statute book.

Although the act restricted who could buy arsenic,

it made no mention of who could sell it.

So inevitably, the deaths continued.

A few years, and many murders later,

Parliament finally introduced further laws

to restrict the sale of the more obvious poisons.

More importantly, they also created the trade of chemists and druggists.

The Arsenic Act and other acts that followed

finally brought arsenic and a whole range of other dangerous chemicals

under some sort of control.

Now, I do think it is gloriously ironic

that it was from all these poisonings, accidents and murders

that the modern, legitimate business of pharmacy emerged.

At the start of the 19th century,

poisons had been mysterious and deadly compounds.

Convenient for killing yourself or others.

By the middle of the century, a more rational understanding

of how they worked was emerging.

And along with a legal and professional framework

designed to control their use,

it would lead to a new era of scientific discovery.

This is belladonna, deadly nightshade.

And there is certainly enough there to kill me.

Now, belladonna in Italian means beautiful lady.

And that's because in the past, elegant ladies

would get the juice from this plant

and they would use it to dilate their pupils

in the hope that it would make them look more attractive.

In the 19th century, they managed to isolate the active ingredient

from the belladonna plant.

It's a substance called atropine.

And ophthalmologists started to use this to help them examine the eye.

Now, I have the modern equivalent here.

And I'm going to put some in my eye to see what happens.

Ooo! That does sting.

Over the last few minutes,

the focus in this eye has gradually gone.

And I think you can tell that my pupil

is a great deal bigger in this eye than that eye.

But am I more attractive?

One of the reasons why having a big pupil

is supposed to make you look more attractive

is because when you look at somebody

and you find them sexually attractive, then your pupils expand.

So it's really just me saying to you,

at this moment, I find you very, very attractive.

And that's why you find me very, very attractive.

Atropine is extremely toxic

and ladies dying to look more beautiful

were at risk of doing just that.

And yet, oddly enough, the best treatment for atropine overdose

turned out to be another poison.

In 1864 in Prague,

a doctor was summoned to treat four prisoners

who had broken into a local dispensary,

and, thinking they were drinking alcohol,

had drunk a large quantity of liquid containing atropine.

When the doctor got there, they had clear signs of atropine poisoning.

The men were seriously ill, lying prostate on the ground,

vomiting profusely, with these huge dilated eyes.

The doctor had no idea how to treat them.

Then an ophthalmologist friend of his suggested something radical.

Poison the men even further.

But this time, with a different poison.

Extract of Calabar bean.

Calabar beans contain a number of pharmacologically-active alkaloids,

one of which is physostigmine,

which constricts the pupils.

Unlike atropine, which dilates them.

The hope was it could also reverse

the other more serious effects of atropine.

The doctor felt he had nothing to lose,

so he took the man who was sickest,

whose temperature had gone up

and who really looked as though he was on the brink of death.

And he got him, not without difficulty,

to consume some of this second poison.

Within a few hours, his temperature had come down.

Within a day, he was completely cured.

Calabar beans and atropine have opposing actions.

They can be used to cancel each other out.

So effectively, one can be used

as the antidote to the other, either way around.

And it wasn't long before poisons began to be commonplace

in a physician's drug cabinet.

In fact these, days, atropine is often used

to reverse the effects of insecticide poisoning

and it's also used to treat some forms of heart disease.

During the 19th century, researchers looking into poisons

were, on the whole, trying to find ways to make them more productive,

more beneficial.

At the start of the 20th century,

things took an altogether bleaker, darker turn.

World War I.

It would leave 17 million people dead or missing in action.

It was a living hell.

And it was made even more hellish by the work of industrial chemists.

And during 1917, troops based in Ypres, Belgium,

reported a strange peppery smell in the air

and a golden, shimmering cloud that surrounded their feet.

Within 24 hours, they had started to itch uncontrollably.

And they came up in horrible, painful blisters

and vile, incurable sores.

Those who had inhaled too deeply started to cough up blood.

The troops had been poisoned by mustard gas.

Gas masks like this one were state of the art at the time,

but they were pretty useless against mustard gas.

The problem is, mustard gas can be absorbed through the skin.

Even if you were fully clothed, you were not fully protected.

Gasping, spluttering, drowning,

it could take up to six weeks to die,

and it was a terrible death.

Now, mustard gas was not the first of the poison gasses,

it was actually one of a number that had been weaponised

by the Kaiser Wilhelm Institute

under the directorship of a man called Fritz Haber.

Fritz Haber was a professor at the prestigious University of Karlsruhe.

And was married to fellow chemist Clara Immerwahr.

Haber would go on to win a Nobel Prize in chemistry,

but he also played a major role in the manufacture of chemical weapons.

He really pressed the Germans, who...

The German military didn't have much regard for science.

..pressed the Germans to see what science could do

in providing them with explosives and chemical weapons,

and he oversaw the first use

of chemical warfare on the Western Front.

He saw it as an efficient way to fight a war.

And he didn't think it was especially inhumane.

After all, he said, death is death, however it is inflicted.

His wife, Clara, pleaded with him to stop working on gas warfare.

He angrily and publicly denounced her as a traitor.

Gas warfare was an horrific, but extremely effective new weapon.

It not only crippled and killed,

but also instilled terror right across the battlefield.

Casualties from the first use were estimated at 5,000 to 10,000 dead,

with many, many more injured.

And Haber was delighted, as were the German military.

Haber was promoted to captain and he returned to Berlin in triumph,

but the couple continued to argue

because Clara was deeply unhappy with what he was doing.

Haber, however, felt that he had an absolute scientific

and patriotic duty to continue working in chemical warfare.

Finally, and tragically, Clara took matters into her own hands.

In the middle of the night,

Clara silently removed her husband's pistol from its holster.

She stepped outside.

And then she shot herself through the heart.

Later that day, Fritz Haber left for the Eastern Front

to oversee the next gas release against the Russians.

He left behind his grieving 13-year-old son,

who had been the one to discover his mother's dead body.

Haber continued to enthusiastically promote the use of poisoned gas.

And his colleagues would go on to develop even more deadly nerve gasses.

One reason why World War I became known as the chemist's war.

But the story of mustard gas does not end here.

20 years later, with World War II looming,

researchers at Yale University's School of Medicine

retreated to their labs to try and create antidotes to mustard gas.

They feared a repeat of World War I.

But what they discovered would lead them

into a very different kind of battle.

Two of the doctors involved were Louis Goodman and Alfred Gilman.

Working these libraries, they delved into the medical records

of soldiers who had been exposed to mustard gas in the First World War.

And what they found, amongst other things, was that these soldiers

had surprisingly low white blood cell count.

This chance discovery would lead to a radically new treatment

for one of our greatest killers. Cancer.

Cancer occurs as a result of mutations in the cells of DNA.

These genetic mutations either promote excess cell growth

or remove the normal safeguards that limit cell division.

Either way, the cell begins to divide uncontrollably.

One type of cell that is particularly prone to mutation

is the leucocyte, or white blood cell.

Goodman and Gilman thought to themselves,

if mustard gas can destroy normal white cells,

perhaps it can also destroy malignant ones.

It was certainly worth a go.

After successful animal trials,

they looked for a human volunteer

with white blood cell cancer to test their theories on.

They found a patient with advanced lymphoma,

known to us only by his initials, JD.

These are JD's original medical notes,

which were lost for nearly 70 years.

And I'm the first person outside the Yale medical community

to lay my hands on them.

They tell a fascinating and poignant story.

JD was a Polish immigrant in his 40s. A metal worker.

He was riddled with cancer and had a massive tumour on his jaw.

When he first came in, the tumour had progressed

to the point where he could not swallow,

he could not sleep at night,

he could not fold his arms across his chest

because the lymph nodes in cancer under his arms were so massive.

And he was really encased front and back by tumour, and up to his face.

And he was just absolutely miserable.

His doctors tried everything they could.

But the prognosis was not good.

They had a case conference and concluded it with this line,

"the patient's outlook is utterly hopeless on the present regiment."

With nowhere else to turn, JD agreed to try the experimental drug,

based on deadly mustard gas.

The notes say that at 10:00am on 27th August, 1942,

they gave him the first injection

of what they call synthetic lymphocidal chemical,

but which was, in fact, nitrogen mustard.

Because of the war, even JD's treatment was a secret.

They couldn't name nitrogen mustard.

In the records, it was simply called, Substance X.

X given at 4:30pm and then again,

X given at 9:30am the following morning.

He received a number of treatments using nitrogen mustard.

And with each one, he became a little bit better.

He could actually sleep at night,

he could swallow, he could eat, he was much more comfortable.

The pain became minimal

and he was absolutely thrilled.

Although not fully understood at the time,

nitrogen mustard works by binding to the DNA of dividing cells.

This triggers the cells' self-destruct mechanism.

Instead of dividing, the cells shut down and break apart.

And the cancer, hopefully, is destroyed.

This was the first time that a drug had been used to treat cancer.

This was monumental.

I mean, it was a huge moment in the history of medicine.

It is the beginnings of what we now call chemotherapy.

And very strange to think that it all started

in the horrors of the trenches of the First World War.

All the chemo drugs that followed

have had the same basic mechanism of action.

They are poisonous to living cells.

If you get the dosing right then you can kill the cancer

without killing the patient,

and in fact, nitrogen mustard is still used for

the treatment of some cancers.

But cancers are persistent.

Even today the prospect for people with advanced cancers is often poor.

For JD, treatment came too late.

To say that he enjoyed a few months

is probably accurate but ultimately he followed a downhill course.

JD, the world's first chemotherapy patient, survived for six months.

There's just one entry for the 1st of December 1942.

It simply says, "Died."

JD died peacefully,

unaware of the impact his life and death would have.

His story pulls the strings of your heart. It really does.

I think that he was a sad person,

with few friends, with a devastating disease

and he made a huge contribution to management of cancer.

So we are grateful to him for that,

and we share his agony at the same time.

The field of chemotherapy,

and indeed the very idea of using poisons as medicines,

poses fundamental questions about toxicity.

How do you decide which substances are poisonous and which are not?

After all, even the ancients realised

that poisonous is a relative term.

"All substances are poisonous. There is none that is not poisonous."

Now, that's according to 16th century doctor

and chemist, Paracelsus.

He goes on to add, "If it's simply the dose which determines

"whether a substance is poisonous or not."

Even water can be lethal if you drink enough of it.

Too much causes brain cells to swell,

which can lead to coma and death.

So how much water would I have to drink for it to kill me?

About seven litres drunk over a few hours,

that would leave me with a 50/50 chance of surviving,

and when it comes to coffee, about 100 would probably finish me off.

And it's not just the amount that matters,

the toxicity of a substance can depend on what species you are.

Now, I absolutely love chocolate. If I were to eat a bar this big

then it would probably make me feel a little bit queasy

but nothing worse.

However, it would be a very different story

if I was a dog like Dolly here.

Because chocolate is very bad for dogs.

Two bars this size on a dog this size, could well be lethal.

The thing is it contains a substance called theobromine.

And theobromine in dogs causes vomiting,

heart problems, and convulsions.

So this is for me and not for you.

Toxicity also varies according to the type of exposure.

Whether the poison just touches the skin or is inhaled,

ingested or even injected.

Nonetheless, it is extremely useful to have a comparative scale

of how toxic various substances are.

One measurable lethality is the LD50,

the lethal dose 50%.

In other words, how much of a substance

would kill half of these mice?

Although now rarely tested on rodents,

the concept of LD50 has stuck.

To allow for size, doses are given per kilogram of body mass.

On a standardised LD50 scale,

water comes in at greater than 90,000 milligrams

per kilogram of body mass.

Pure alcohol is fatal to half the population

at 7,000 milligrams per kilogram.

While caffeine weighs in at 192.

Arsenic has an LD50 of 14, curare is lethal at only 0.5.

So while anything can be poisonous,

substances with an LD50 less than 100 milligrams per kilogram

tend to be called poisons.

On this scale most chemotherapy agents, including nitrogen mustard,

would register between one and four milligrams per kilogram.

By the 1950s, researchers had turned some poisons

into effective drugs.

Natural plant poisons like curare were being used in surgery,

and synthetics like nitrogen mustard,

were having an impact on cancer.

They were just a small part of a new enthusiasm

for pharmaceutical products.

But in this dash for cash, the authorities overlooked the fact

that while poisons can be medicines, medicines can also be poisons.

It was only a matter of time before something went badly wrong.

Amongst those rushing out new drugs, was a German company

called Chemi Grunenthal.

Staffed by many former Nazis,

they were searching for lucrative new medicines

and had created a chemical

that looked particularly interesting.

Structurally, the drug was very similar to barbiturates,

a class of drug that was then widely being used

by anyone who had a sleep disorder.

So the company decided to send it off to doctors

and get them to try it on their patients who had sleeping problems.

The new drug did well, and was soon being heavily marketed

as effective against insomnia, coughs, colds and headaches.

Oddly enough, it was a sedative

but it was also known to be quite useful in morning sickness

for pregnant women.

It was distributed initially

under the brand name Distaval.

By 1960, Distaval was sold throughout Europe,

South America, Africa, Canada and Australia.

Around this time the number of babies being born

with deformed or missing limbs and organs,

well, they started to rise.

Initially just a few, but then the numbers took off.

Now this was clearly really distressing,

and something was going on. The problem was, the doctors

didn't have a clue what.

Several traumatic years passed before the cause was finally found,

when a young Australian doctor

looked at the mothers rather than the babies.

The only thing he could find was that these women had all suffered

from morning sickness in their early months of their pregnancy.

And they had all been prescribed the drug Distaval,

which is now more commonly known by its generic name,

Thalidomide.

It has been estimated that around 10,000 babies

were severely disabled by Thalidomide.

Half of whom failed to live to adulthood.

The situation in America, however, was very different.

It was 1960, the year before the link between Thalidomide

and birth defects would be made.

Frances Kelsey was just starting out her new job

as the Food And Drug Administration.

Her first assignment was to review an application

to market Thalidomide.

Since it was already on sale in the rest of the world,

and since no-one yet knew that it caused birth defects,

it should have been a case of simply approving it.

But Kelsey strongly felt the application was not up to standard.

Here's a person who was very well trained in pharmacology,

and medical practice.

And so when she saw the application she was kind of appalled.

It struck her more as testimonials than good solid clinical research.

And she sent a letter responding to the application

saying that in its present form it could not be accepted

and to submit additional data.

Another application was submitted to the FDA

But Kelsey was still not convinced by the safety data.

So despite mounting pressure from the manufacturer,

she again refused Thalidomide a licence.

There was a back and forth between FDA and the mail company.

The mail company was getting quite annoyed, honestly,

threatening to go not only to the supervisor,

the head of the Bureau of Medicine, but the Commissioner of FDA.

But she stood her ground.

She stood her ground as a scientist,

she stood her ground as an FDA official

who of course had to uphold the law,

and the law required that the drug had to be safe.

She persevered through this whole process.

Kelsey continually refused to allow Thalidomide a licence.

When in 1961 the facts finally came out,

Americans appreciated just how close they had come to sharing

in what was by then a worldwide tragedy.

Frances Kelsey was given an award by John F Kennedy,

in recognition of her outstanding work.

Thalidomide was eventually withdrawn

from the worldwide market.

The fact that this tragedy was allowed to happen

and go on for so long, emphasises how little control many governments

actually had over medicines just 50 years ago.

In Britain, for example, the Arsenic Act,

and the acts that followed it, had put existing drugs

and chemicals under some sort of control.

But there was still no effective regulation

of newly discovered drugs.

After the Thalidomide scandal, new laws were passed here

and in other countries, which meant that in future,

drugs had to be safe, they had to be effective,

and doctors also had to tell their patients

if they were being given something experimental.

Because astonishingly enough, before then,

a doctor could give you pretty much what he or she wanted,

and they didn't have to tell you.

These days, pharmaceutical companies wishing to launch a new drug

have to go through multiple clinical trials,

to demonstrate that their drug is safe and effective.

It can take years and cost billions of pounds.

But it's only by doing this sort of rigorous testing

that you discover if a drug has significant toxic side effects.

The broader impact of Thalidomide,

it essentially creates eventually a gold standard

for how drugs should be evaluated.

Thalidomide led to much tighter regulations, which was a good thing,

but the story of Thalidomide does not end here.

Thalidomide seems to cause birth defects

by blocking the creation of new blood vessels.

Growing limbs are particularly vulnerable.

It is clearly a very dangerous drug.

Yet this notorious chemical has been found to have beneficial effects.

For example, when it was given to people with Leprosy,

their skin lesions turned from this...

..to this, literally overnight.

And it's also being successfully used

on a particularly hard to treat form of cancer, multiple myeloma.

The rise and fall and rise again of Thalidomide

illustrates just how tricky medical research can be.

In one context a drug could be a poison, in another a life-saver.

Despite the challenges, and with tighter regulations in place,

medical research continues apace.

While some still focus on mineral and plant poisons

or build synthetic ones,

others are now driving forward,

into the dangerous world of the microbe.

Although they are only microscopic,

microbes can produce toxins which are real heavyweights.

And the ultimate microbial poison we have purified and tamed,

is a toxin produced by the microbe Clostridium botulinum.

Botulinum toxin is the most poisonous substance known to man.

Now, a couple of teaspoons full would be enough to wipe out

every person in the UK.

And a couple of kilos would kill every human on the planet.

Fortunately, this is sugar,

but I do have some botulinum toxin -

better known as Botox - over here.

Only a few nanograms, but it is botulinum toxin none the less.

The toxin is produced by bacteria,

and was first discovered in poorly prepared sausages during the 18th century.

It was named after the Latin for sausage, botulus.

On the LD50 toxicity scale,

Botox measures just 0.000001 milligrams per kilogram.

The deadliest of the deadly.

A lethal dose for me, weighs less than one cubic millimetre of air.

Botulinum toxin, like curare,

commonly kills its victims by causing respiratory failure.

But unlike curare, you're not going to be able to keep someone alive

with a pair of bellows.

Because botulinum toxin lasts much longer.

You have to keep them on a ventilator for weeks, if not months.

Botox works by preventing muscles from receiving nerve signals.

Botox is an enzyme which enters the nerve and destroys vital proteins.

This stops the communication between nerves and muscles.

Only the growth of new nerve endings can restore muscle function,

and this can take months.

Botox is a neurotoxin, which means it destroys nerves.

Oddly enough, that makes it useful for a number of medical conditions

ranging from eye squints, to migraines,

from excess sweating, to leaky bladders.

But its main use, of course, is ironing out wrinkles in ageing faces

and it does this by destroying the nerves that cause frowning.

The quantities used are absolutely tiny,

a few billionths of a gram dissolved in saline.

In the name of science, I tried botox a few years ago.

-It wasn't painful, was it?

-No, no.

It certainly smoothed away the wrinkles.

But it also gave me a weird expression

until the new nerve endings grew back.

It may not be to everyone's taste,

but botox is certainly big business.

Costing around a hundred trillion pounds per kilo,

botox is the most expensive product on earth.

Huge amounts of money can clearly be made from new medicines,

so it's no wonder that the search for them continues.

Having started out by collecting exotic poisons,

extracted from plants, such as curare, we've come full circle.

As well as microscopic life, researchers are intensely

interested in studying some of the other ingenious killers of the natural world.

Killers that scuttle, slide and slither.

In this room there are over 250 snakes, spiders, scorpions and other venomous creatures.

Their venoms have evolved over millions of years

and they're all different.

The hope is that amongst this lot,

there are some which could lead to a significant medical breakthrough.

One of the greatest medical challenges is still cancer -

particularly, cancers of the brain.

Brain tumours like this one here, can be quite difficult to treat.

If you use radiotherapy, chemotherapy, you risk damaging healthy tissue.

If you can get at it and cut it out then that's good,

but also it's quite difficult sometimes to tell the difference

between tumour and healthy tissue.

Surgeons face a real dilemma in how much of the surrounding tissue they should remove.

Even though on a scan you may see a tumour,

that looks let's say 2cm in size,

we know that there are tumour cells several centimetres away

from that ball of tumour.

So to entirely remove everything you would need to be able to remove

all that surrounding tissue, most of which is normal brain.

Removing healthy brain tissue

could mean the difference between walking and not walking,

seeing and not seeing,

talking or being mute.

And so being able to pinpoint unhealthy tissue, is critical.

Which is where venomous animals may be able to help.

This is Leiurus quinquestriatus, also known as the death stalker.

As her name implies, she is a particularly venomous scorpion.

A single sting from that tail

could probably kill a child or an elderly person,

although probably not kill me,

it would certainly be excruciatingly painful.

The venom of this scorpion contains a powerful cocktail of neurotoxins,

chemicals that poison brain cells and nerve cells.

One, is called chlorotoxin.

Chlorotoxin affects the nervous system of insects,

utterly paralysing them.

But when trialed in human tissue,

it did something completely different.

It seemed to have a special affinity for cancer cells.

The compound bound to the tumour, and avidly bound -

in other words, once it's stuck, it stayed stuck.

Chlorotoxins from the scorpion venom bind tightly to receptor sites

on the surface of the cancer cells.

These are called Annexin A2.

Unfortunately the chlorotoxin is not strong enough to actually kill the cancer cell.

However, when it's mixed with a fluorescent dye,

it highlights cancer cells,

allowing surgeons to avoid cutting out healthy brain tissue.

It can be visually extremely difficult to differentiate tumour

from normal brain, they look alike they can feel alike.

So the ability to fluorescently identify areas that are abnormal

based on the fact that they bind chlorotoxin,

and then remove that tissue, is extremely appealing.

So in the operating room, we would simply switch our imaging system

to a system that shines infra-red light,

and just look at the picture we see.

The areas that light up blue, should be just tumour,

so you can detect microscopic amounts of tumour.

It's promising research,

and just one area where this venom could offer medical benefit.

It's been a long process and development,

lots of twists and turns

but, yeah, I'm looking forward to where the future goes with this.

It certainly has the potential to be very, very promising.

Animals produce a huge range of different venoms,

and many have been shown to have remarkable properties.

Venom from snakes has led to the production of a new type of anti-hypertensive drug,

for treating high blood pressure,

while the lethal cone snail

has produced one of the world's most powerful painkillers.

So who knows what other medicines might be lurking in the fangs of the creatures behind me?

Venoms are particularly appealing to modern researchers,

because they tend to be very specific.

They seek out precise targets,

which ties in well with another medical revolution that's going on.

It, too, builds on the idea of targeting -

but this time it's targeting at a genetic level.

Medicine is getting truly personal.

The trouble with dishing out the same drugs to everyone,

is that we are all different,

a drug that lowers my blood pressure might have absolutely no effect on yours.

So how close are we to creating truly personalised medicines?

What we've found as we've sequenced the genes of a number of people,

is that everybody has slight variations and subtle changes

in their genes,

and these dictate ever-so-slightly subtle differences

in the way that cells respond to drugs.

The concept is that we use that information

to really tailor a specific therapy for that one person.

We're doing it to some extent already.

Right now, we can sequence relevant bits of the person's cancer genome,

for about the same cost as many of the scans we do for patients with cancer.

The similar sort of cost as the pathologist looking down the microscope

at the slides from that person's cancer.

So I think it's very likely that over the next 5 to 10 years or so,

these kinds of genetic approaches will make their way into the clinic.

Personalised medicine is set to be the next big step

in a process that started in the early 19th century.

Since that time, our medical world has been utterly transformed.

We no longer expect to die young,

instead the threat comes from diseases of old age like cancer.

Here poisons have proved to be particularly useful.

Even arsenic, the murderer's friend,

has now found a medical use, as an anti-cancer agent.

Thanks to medical pioneers, we now know how to control pain,

infections are not the death sentence they once were.

And doctors use many poisons on a daily basis.

200 years ago, there were very few effective treatments.

Now, doctors are talking about targeted, specific, personalised medicines.

We have come a long way, but we still have a long way to go.

If you'd like to take part in a quiz on pain,

or perhaps find out something more about pus and poison,

then go to the website below

and follow links to the Open University.

Subtitles by Red Bee Media Ltd