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

This programme contains scenes which some viewers may find upsetting.

On Saturday, the 14th December 1799,

George Washington, one of the founding fathers

of the United States of America, lay dying.

A couple of days earlier,

he'd been out riding in cold and wet weather.

He developed a sore throat.

Early on the Saturday morning, he said to his wife,

"I'm feeling very ill."

Within hours, his personal physicians had arrived.

The finest in the country, the best money could buy.

They had all sorts of

suggestions as to what was making him ill.

His humours were unbalanced

or perhaps he breathed in miasmas - foul air.

His doctors gave him the standard medical treatment

for someone who was as severely ill as he obviously was.

They took a knife, found a vein and bled him repeatedly.

They drained him of more than four pints of blood.

By nightfall, Washington was fading fast.

So his physicians applied even more scientific treatments.

This Spanish fly, although it's actually a green beetle,

they would have ground it up,

and then applied the paste to his throat.

But all that did was blister the skin.

He said to his doctors,

"I die hard, but I am not afraid to go."

By late that evening,

the first President of the United States was dead.

Washington probably died from a simple infection.

At the end of the 18th century,

it made no difference if you were a pauper or the president.

What you got was little more than quackery.

But that was about to change.

On the other side of the Atlantic, new ideas were

beginning to prise open long-closed medieval minds.

This series tells of the quest to find drugs that actually work.

Drugs which could be harnessed to switch off pain.

That's a very, very weird thing to do.

Poisons from the natural world that we could turn to our advantage.

All poisons should be considered as potential medicines.

In this programme, I'll be telling the extraordinary stories of those

who fought an enemy, armed with weapons

more savage than anything we could dream of.

People frequently died of infection and things like purple sepsis,

women died after delivering their children.

We know that during the First World War,

more troops died because of wound infection

than because of direct hits by enemy fire.

This is the story of how we learnt to fight back,

and by doing so, changed the course of human history.

This place is a Category A prison.

It houses the worst mass murderers in history.

Serial killers who have been responsible

for the fall of empires and the death of kings.

I'm not going to be allowed to get too close to these inmates

because they are extremely dangerous

and are kept under constant 24-hour, state-of-the-art surveillance.

If they escaped, the results would be disastrous.

The Centers For Disease Control And Prevention, in Atlanta,

is not for those of a nervous disposition.

It holds some of the world's most deadly life forms.

CDC has thousands of scientists who work 24/7

figuring out what's making people sick and how to stop it.

This facility contains some of the greatest evils

ever collected in one place.

This bacteria causes the plague.

Your flesh dies and rots while you are still alive.

The Black Death of the 14th century

killed a quarter of Europe's population.

And then, there's tuberculosis,

a slow and deadly killer.

The creator of oozing lung abscesses.

The poet Keats, all three Bronte sisters

and Chopin are a few of its more artistic victims.

And this is gangrene,

caused by any number of bacterial infections

that lurk unseen in every dirty bullet, scalpel, and delivery ward.

Some bacteria don't need a wound to get inside you,

they're already there, waiting patiently.

Patiently for our defences to drop, and then, they pounce.

That's probably what did for George Washington.

In 1790s America, sudden death was utterly common,

and you clustered round people's bedside

when they got cold and when they got chills because they could die.

Washington's doctors would have laughed in your face

if you had told them that microscopic life was killing him.

They still clung to theories passed down from the Ancient Greeks.

They believed that if you had a disease,

the humours were out of balance.

If you had a fever,

you were considered to have an excess of the blood sugar,

well, you were flushed, after all.

So, why did it change?

How did we track down, trap, destroy and isolate our enemies?

Two bitter rivals would throw light on an invisible world of microbes,

an idea called germ theory.

But the starting point was not doctors, patients,

any of the obvious.

It began in the vineyards of France,

and the problem of how to get a decent drink.

In the mid-19th century,

The French wine industry was undergoing something of a crisis.

Now, this is what good wine is supposed to look like, smell like

and, um...taste like.

This wine looks fine, doesn't smell great...

Ahh, it tastes absolutely vile.

Now, the English were complaining a lot about the fact

they were being sold this expensive vinegar,

and the French were understandably keen to find out what was going on.

What is it that makes some wine go off so spectacularly?

It was a question of national pride,

so the emperor Napoleon III

asked a local chemist, Louis Pasteur,

to find a solution, and quickly.

When Pasteur looked down his microscope,

at the off wine,

he saw something there that was not present in normal wine.

Microbes.

He reasoned they must be spoiling it.

So true to his emperor's demands,

he set out to destroy them.

First, he tried boiling the wine,

but after boiling, it tasted almost as bad as when it was off.

It does not taste great.

So what he had to do was,

he had to get the temperature just right.

It had to be hot enough to kill the bacteria,

but not so hot that it would spoil the wine.

And after much experimentation, he found the ideal temperature.

55 degrees Celsius.

So he was happy,

the Emperor was happy, and this technique,

pasteurisation, became widely used.

But the really important thing about this whole wine demonstration

is it got Pasteur thinking.

If microbes can cause wine to go sour,

what effect are they having on people?

Now, before he could really develop these ideas much further,

he was scooped, by an unknown, a younger man,

and what was worse, he was German.

Nationalism was fed by the Franco-Prussian War

of the early 1870s,

a short, bitter and brutal conflict.

With the fighting over,

the victorious German soldiers headed for home

or started looking for new employment.

In 1872, a young German doctor, Robert Koch,

arrived here, in Wolsztyn.

It's now Polish. Back then, it was a small rural town in a

remote part of Prussia.

Koch had served as a surgeon in the war,

and before that,

studied medicine at one of Germany's finest universities.

He may have found himself a humble medic in the back of beyond,

but he had ambitions.

Robert Koch and Louis Pasteur were, at first, friendly rivals.

But with the war between the new German Empire and the French,

it became rather unfriendly.

Koch was keen to go one better than Pasteur,

Prove that microbes make people ill,

but how was he to do that, stuck in the middle of nowhere?

And then, on his birthday, he got a present from his wife,

an expensive one, and that changed everything.

Now, when I was ten, I got a microscope,

I wasn't particularly thrilled,

but for Robert Koch, this really opened up the world,

albeit a microscopic one.

Now, all he had to do was find something to look at.

And that's where this rural location came into its own.

Because the fields around Wolsztyn were filled with sheep

suffering from anthrax.

A disease which killed tens of thousands of them every year.

But what was bad news for Prussian farmers

was good news for Robert Koch,

and with the help of a local butcher,

he had an ample supply of infected tissue to take here, his home.

So he's got the microscope from his wife

and he's got some infected animal matter from his friend, the butcher.

What he does is he takes a sample,

and he smears it on a slide,

and then, he looks at the slide

under the microscope.

And we know what he saw, because he drew them,

and these are original sketches.

These funny little grain-like particles here,

these are anthrax bacteria.

So far, so ingenious.

But what he really needed to do was to prove it was the bacteria

that had killed the animal. How was he going to do that?

Well, what Koch did is he transferred bacteria from the

infected spleen and meat into the animal's eyes,

and there they grew in this sort of rich jelly medium.

And when he had a lethal dose, what he did is he took a mouse and he

deliberately infected the mouse with bacteria from the eye.

And then he waited.

Well, the mouse died, and with it died miasma theory,

that age-old nonsense that it is bad air that causes infections.

It clearly wasn't bad air that killed the mouse, it was bacteria.

Miasma theory was replaced by germ theory,

a new way of looking at disease.

When hostile bacteria invade a living organism,

they quickly multiply,

producing toxins and enzymes which

poison and destroy the tissue around them.

If the body's natural defences are overrun,

the result can be death.

I think Robert Koch is rightly thought of, along with Louis Pasteur,

as one of the founders of modern medical microbiology.

Koch was important both for

discovering the microorganisms that caused diseases,

and also for generating an intense and very real

sense of excitement that medicine

was finally about to get to grips

with problems that, really, humanity had been able to do nothing about

since we first stepped onto the world.

By the end of the 19th century,

Pasteur and Koch had, between them,

identified many of the microbes that cause the worst diseases.

From anthrax to typhoid, cholera to TB.

What we didn't yet have

was a drug that could safely and reliably treat infection.

When one came, it would be from a most unexpected source.

The need was certainly there.

At the start of the 20th century, diseases you might have associated

with medieval times were still rampant.

Syphilis, for example.

Now, for centuries, doctors had used mercury to treat it,

but being extremely toxic, it tended to kill the patients.

So when, in this Frankfurt mansion, a scientist called Paul Ehrlich

set out to find a safe and effective drug against syphilis,

it was a major challenge.

Fortunately, he was a real obsessive.

Paul Ehrlich studied medicine in the early 1870s,

but he spent an awful lot of time in the laboratory

rather than the clinic, where he should have been.

One of the things Ehrlich was doing

was playing around with artificial dyes.

The first had been discovered in 1856

and soon, people went dye-crazy.

His favourite colour was methylene blue,

and with this, he made a remarkable discovery,

one which would set him on the path to medical greatness.

Ehrlich was wonderful in showing how

you could use dyes to illuminate the hidden world.

The world which, even down a microscope, you wouldn't be

able to see unless you coloured it

with these dyes that showed physical processes.

He spent, wasted, whichever way you want to look at it,

a lot of time playing around dying regions of biological tissue.

When Ehrlich added a drop of methylene blue

to tissue infected with bacteria,

he noticed something astonishing -

only the bacteria was stained by the dye,

not the tissue around them.

Often, what was needed to discover these bugs was the right stain.

Get the right stain and in amazing colours,

these bugs would appear before your very eyes.

Now, the fact an artificial dye will selectively stain bacteria

was remarkable, but it's what Ehrlich thought next

that was truly revolutionary.

What he did was he noted that some compounds were toxic

and he said what if you create selective toxicity

so that you can give somebody a compound that will kill off

what's making them unwell and leave them unharmed?

And he famously coined the phrase from a German folk story,

you could create these "magic bullets",

which is what we've been trying to do ever since.

Now, many people thought Ehrlich was wasting his time.

But he was convinced that magic bullets existed

and he would discover them.

Initially, he tried finding a cure for sleeping sickness.

But with the help of his Japanese assistant, Sahachiro Hata,

he switched his attention to a pathogen

that was rather more common in Germany.

Common, but horribly disfiguring.

Syphilis.

The end stage of syphilis was pitiful -

paralysis, insanity and then, death.

There were no cures and the only treatment, mercury,

made your hair and teeth fall out,

before eventually destroying your entire nervous system.

Ehrlich hoped to find a magic bullet that would be more selective,

poisoning the bacteria but not the rest of the body.

Ehrlich thought that arsenic might

be effective against syphilis.

Arsenic is notoriously poisonous, but by this point,

German chemists had made hundreds of different compounds of arsenic.

So Ehrlich asked his assistant Hata

to work his way systematically through them,

hoping that, amongst them, there would be one

that was safe and effective.

Hata had found a way to infect rabbits with syphilis.

He now set about the unenviable task

of testing arsenic compounds on them, one after the other.

Some compounds killed both bacteria and rabbit.

Some killed neither.

Hata went through hundreds and hundreds of compounds

until, finally, he found one that was rather special.

Compound 606, it killed the bacteria, but best of all,

it left the dear old rabbit intact.

This was the magic bullet they had been hoping for.

Salvarsan 606 showed that Ehrlich was right,

that these things were out there,

all you had to do was methodically screen for them and you would find them.

It showed the power of methodically screening lots of compounds.

606, 606 compounds, to see what worked.

I do think it's wonderful that it was in this building, 100 years ago,

through a combination of luck, logic and sheer hard work,

that they eventually found a cure for syphilis,

a disease that had destroyed the lives of countless millions.

Newspapers at the time carried it on the front pages.

The medical profession were stunned.

To be able to treat syphilis was miraculous, absolutely miraculous.

By the 1920s, Salvarsan was the world's most popular drug,

particularly with men.

But Ehrlich's hope that it would be just the first

of many magic bullets proved ill-founded.

Infections caused by the most minor

of injuries were still uncontrollable.

People frequently died of infection

and things like purple sepsis,

women died after delivering their children.

Septic wards were gruesome places,

filled with the sick, the dying and the desperate.

There were people with severe and chronic infections who tended to be

there for sometimes weeks,

with pots under their beds draining the pus

from various abscesses or infected wounds.

Cleaning of the wound of pus was the only way doctors,

or more likely nurses, had of fighting infection.

Pus is the debris left behind when

the white blood cells of our immune system

take on invading bacteria.

But it can also become a nice cosy home for the bacteria,

a constant source of reinfection.

By draining pus,

doctors hoped to prevent infections reaching the blood.

Because once that happened,

the prognosis becomes incredibly bleak.

Half of those who went into a septic ward

never came out alive.

But that would change, thanks to the chance discovery, in 1928,

of a mould with remarkable antibacterial properties.

Penicillin.

Most people learn at school that it was Alexander Fleming

who was responsible for penicillin.

Well, this is only partially true.

Alexander Fleming, he'd hailed from Scotland,

he was a very bright student.

Eventually, he won a scholarship to St Mary's Medical School

and prospered there,

and stayed on at St Mary's because he was a good sportsman

and he particularly was a good shot,

and they wanted him for their shooting team.

When he wasn't shooting, Fleming spent much of his time in the lab,

studying staphylococci, bacteria that are commonly found on skin.

Then, in August 1928, Fleming went away on holiday.

When he returned,

he started to examine some Petri dishes

which he'd previously seeded with bacteria.

And he noticed something very odd.

An uninvited fungal mould.

Well, I want to show you the original cultivation, which I kept.

Here's the mould and above,

you've got the staphylococcal colonies,

but closer on the mould,

the colonies have disappeared.

Normally, bacteria grow new cell walls before they divide.

But the mould produced a substance

that prevented new cell walls being made.

The bacteria were unable to divide

and eventually burst open, like a balloon.

Fleming was lucky, it was likely the penicillin mould had

blown in from a nearby lab, where they were studying fungi.

But contrary to legend,

he really didn't make the most of his remarkable break.

He didn't really realise what he was on to.

He made one very short comment in his first paper

that said maybe this could be injected into the sites of infection,

but he never did that himself and he never followed it up.

So I have him down as an acute observer,

but not the genius, as he's often been portrayed.

It also didn't help that he was an absolutely terrible public speaker

and was completely unable to enthuse others.

For these reasons, the most powerful lifesaving fungus

the world has ever known,

well, for many years, it just languished in the dark.

And there it would remain until 1938,

when researchers here, at the Dunn School of Pathology, in Oxford,

would rediscover penicillin,

and turn it from a medical curiosity

into the greatest lifesaving drug the world has ever known.

The storm clouds of the Second World War

were beginning to gather over Europe,

20 years after the end of the First.

We know that, during the First World War,

more troops died because of wound infection

than because of direct hits by enemy fire.

In Germany, scientists had discovered the antibacterial

properties of the sulphonamides.

And with the prospect of more bloodshed on the horizon,

a small team was assembled in Oxford

to find a British germ-killing agent.

The team had stumbled across Fleming's original penicillin paper

and by remarkable chance,

there also happened to be some penicillin mould in the building.

The team consisted of three very different characters,

led by an abrasive Australian doctor called Howard Florey.

This was his office.

Florey's talent was as a team leader and a designer of experiments,

and he was the guy who'd organise the team

and brought in the various specialities.

He recruited two very different assistants.

Ernst Chain, an excitable Jewish refugee who'd fled the Nazis.

And Norman Heatley, a keen sailor from Suffolk.

So Chain trained originally in Berlin and was generally regarded as

a high-class biochemist.

Heatley was an expert at micro techniques

and he was very good at making equipment,

producing things out of bits of wood and bits of rubber tubing.

In 1939, war broke out in Europe.

With wounded British troops dying in France,

there was mounting pressure on the Oxford team to come up with answers.

Trouble was, penicillin was proving hard to grow,

and even harder to purify.

Unlike Fleming, Florey's team had

managed to extract the active chemical.

And they had tested it on bacteria.

Now, they needed to test it on a living creature.

In this lab, in May 1940,

they did the first really important experiment.

They got eight mice

and injected them with a lethal dose of streptococcus, a bacteria.

And then, they injected four of the mice with penicillin

and waited to see what would happen.

Well, Norman Heatley kept a diary and this is what he wrote.

"I stayed at the lab till 3:45,

"by which time all four control animals were dead.

"The ones given penicillin, however, were all still alive."

Now, I'm sure Heatley recognised this was a massive moment,

that what he wrote in his diary was,

"I discovered I had put my pants on back to front -

"a lucky omen."

Florey was more obviously enthused,

saying it looked like a miracle.

And this was not hyperbole.

Never before had anyone seen an effective germ killer

with so few side effects.

But the team now had to find ways to produce enough of it

to test on a human.

Florey made the comment that humans are 3,000 times bigger than mice,

and so, we're going to need 3,000 times more penicillin

than we had for these experiments.

And so, during the summer of 1940, as France fell to the Germans,

and Britain feared invasion, the entire staff

of the Oxford School Of Pathology,

was enlisted to help make penicillin.

With, amongst other things, bedpans.

Trying to make larger amounts of penicillin, in this building,

with very little money and in the middle of a war,

was an absolute nightmare.

What were they going to do about equipment?

Well, they had to improvise.

They found they could grow the penicillin mould,

in bedpans and then skim it off.

It was a real Heath Robinson affair,

made out of a bath, milk churns, an old book shelf,

apparently from the Bodleian Library,

and they made pretty rapid progress.

But before seeing if it could cure,

they needed to make sure it wouldn't kill.

Just because it worked in mice

didn't mean it would work in humans.

They needed someone prepared to take a potentially fatal dose.

Mrs Elva Akers, a 50-year-old housewife, was asked to help.

She had terminal cancer,

and she was told that the penicillin would do her absolutely no good.

It might indeed push her over the edge.

Nonetheless she volunteered, saying she was proud to help.

The penicillin used was extremely impure.

I think we now know that what went into the first patient

was about 3% penicillin, 97% impurities.

On the night of January 27th 1941,

Elva became the first human to be injected with penicillin.

After a few days, the team concluded it was safe.

Now they needed to find a patient it could actually help.

Just a few doors down from Elva, in the same hospital,

a man was fighting a particularly hideous infection.

It had started following a minor accident.

Albert Alexander, a 43-year-old police constable,

was out gardening one day when he got scratched

on the side of his face by a rose thorn,

or at least that's how the story goes.

Whatever caused the tiny wound,

it soon became horribly infected

and Albert was consigned

to one of the hospital's notorious septic wards.

This is Albert, healthy, good-looking young man,

and this is Albert in hospital.

He's a complete wreck.

His left eye has gone, he's covered in abscesses,

and his lungs are full of purulent matter.

This is draining pus from his right eye.

He really only has one hope - penicillin.

On February 11th, 1941, Albert was given the first dose.

Over the next few days,

Florey and his team constantly monitored

him for any sign of improvement.

He made what seemed to be a remarkable recovery.

He was... His temperature came down,

he started to eat,

I think he even got out of bed. He was much better.

The penicillin was clearly working, which was fantastic.

Unfortunately, they didn't have enough of it.

So in desperation, they collected his urine,

and extracted from it

the penicillin that his body hadn't used.

But it was all too little, too late.

A month after starting treatment, Albert Alexander died.

Sad though the death of Albert was,

his initial dramatic recovery suggested

penicillin could be the miracle drug the country needed.

And one of the fears now was that it might get into German hands.

Penicillin was extraordinary stuff,

but these were also extraordinary times.

There was a serious fear that Britain would be invaded

and if so, they would have to destroy all their work,

rather than allow it to fall into enemy hands.

So they smeared spores on the inside of their coats...

So that if they were forced to escape from Oxford,

they could actually take the mould with them

and start the work again.

So that gives some sense of the

importance that they ascribed to this work.

The conviction of the group

was that their discovery was so important,

it was a potentially capable of changing the course of World War II.

But if the entire Dunn School working for months

couldn't make enough of the stuff to save one man,

then it wasn't going to help anyone.

So that was why Florey realised the importance of upping production,

but in fact, he couldn't get the

British pharmaceutical industry to become involved.

They were fully occupied doing things for the war effort.

Um, and so, in a sort of frustration,

he decided he'd have to go to America.

In July 1941, Florey and Heatley arrived in New York,

carrying the penicillin mould in a briefcase.

They told immigration they were on medical business.

With the help of the Rockefeller Institute,

Florey and Heatley were introduced

to the country's biggest chemical companies.

Unlike their British counterparts,

they quickly realised the drug's potential.

The war was causing casualties that led to infections that led to death.

Penicillin clearly was a winner,

the question was, can we get it to the troops

in sufficient quantity and in time?

Now they were here, there were three problems they needed help solving.

Firstly, find something the mould really liked growing in.

Secondly, find a more powerful strain of the mould,

and finally, improve the production process.

Well, the first problem was soon solved because it

turns out that penicillin mould really likes this stuff, corn syrup.

Sweet, and sticky.

They like it almost as much as we do.

And fortunately, the Americans had lots and lots of it.

The other two problems were rather harder to crack.

The problem with the penicillin mould they were using

was it was still based on Fleming's original mould.

Maybe there were even more powerful moulds

which could produce more penicillin?

An international search was launched,

and samples of mould found anywhere and everywhere in the world

were flown to the US labs by military transport.

Scientists worked around the clock testing them,

but none gave the yields needed.

Perhaps a more powerful strain simply didn't exist.

And then, there was a wonderful twist.

Now, the story goes that a woman called Mary Hunt,

who worked for the US Department of Agriculture,

was wandering through the fruit markets, as she often did,

looking not so much for fresh fruit as for something really rotten.

And one wonderful day, she came across this.

A mouldy melon.

And they took this off to be tested

and it turned out that the mould was

a really powerful source of penicillin.

So much so that, for a while,

it became the source of almost all the world's penicillin.

But despite these improvements,

the inefficiency of the actual production process,

meant that by 1943, there was still

only enough penicillin to treat a lucky few.

The standard techniques were large wide-bottomed flasks,

because you had a single layer of mould producing,

the yields from each flask were minimal.

And the need for penicillin had never been more urgent.

D-day, the greatest amphibious invasion in history,

was only months away.

Casualties were going to be horrific.

Penicillin was the US military's second top research priority,

after the Manhattan Project, after nuclear weapons.

It was then that a small chemical company

based in this building in Brooklyn, called Pfizer, got involved.

Now, these days, Pfizer is better known

for its anti-impotence drug, Viagra.

But back then, they produced citric acid, used in fizzy drinks.

Now, they realised, as everyone else had,

that if you just grow penicillin on the surface of a liquid,

then that is going to be really inefficient.

What you want to do is grow it throughout the liquid.

The problem is, that penicillin needs oxygen to grow,

so they came up with a solution which they hoped would work.

The oxygenation came with a tube introduced into the medium,

into which oxygen was pumped.

But you couldn't put too much and you couldn't put too little,

so learning how much was right was key.

There was absolutely no guarantee the technique would work.

But the company took a gamble.

Because of war-time shortages,

they had to convert an old Brooklyn ice factory,

scrounging a boiler from Indiana and a lift from Long Island.

With just two months to go before D-day,

they installed 14 giant fermentation tanks.

Then, they added the corn syrup,

and the cantaloupe mould before turning on the air.

The results were spectacular,

they soon began producing five times

as much penicillin as originally planned.

By June 1944, the D-day invasions,

there was enough penicillin for every injured soldier,

and most of it was produced right here,

in the Pfizer plant in Brooklyn.

Penicillin was successfully developed in time

to hugely influence the outcome of World War II.

Protracted hospitalisation from infected wounds

was almost eliminated amongst Allied soldiers.

Many could be back on the front line

with a rifle in their hand within weeks.

For others, it made once-lethal wounds survivable.

NEWSREEL: 'Thousands of men, thanks to penicillin,

'will come home to their thankful families.

'Science has won another victory over death.'

Hopes were high, and largely justified.

These pictures show a little girl going from death's door

to happy in just a few days.

No longer would a scratch from a rose thorn or a minor cut

lead to a hideous death.

Now, it all started with Alexander Fleming and his chance observation,

but without Florey and the Oxford team,

who knows when the mould would have

been made into a safe and effective drug?

In summary, I would say that the work of Florey's team,

particularly Florey, Chain, Heatley,

resulted in the greatest medical advance of the 20th century

and gave us a new way of looking at

the treatment of infectious diseases.

Penicillin heralded the dawn of the antibiotic age.

And in the years that followed,

further antibiotics were discovered and developed

that made the incurable curable,

and changed what was once fatal into no more than a minor illness.

Prior to antibiotics, prior to penicillin,

we really did live in a world where

you could be young, fit and healthy one day,

get a cold the next, and be dead by the end of the week.

For the first time in human history,

we seemed to have the germs on the run,

but the battle against bacteria represents only a part of the story

of our fight against infection.

Because antibiotics, spectacular though they are,

are useless against viruses.

And viruses, in many ways, presented an even greater challenge.

And that's why, along with all the deadly bacteria

held here, at the Centers For Disease Control,

there's also a wing for viruses.

In fact, some of the tightest security is for them.

Until just over a century ago,

nobody knew that viruses actually existed.

And it wasn't until the 1930s,

with the invention of the electron microscope,

it was actually possible to see them.

Viruses are up to 100 times smaller than bacteria,

and far, far simpler,

essentially, no more than a tiny piece of genetic material

surrounded by a protein coat.

They're the most numerous biological entities on Earth,

able to infect animals, plants and even bacteria.

But they cannot exist on their own.

They need to invade a living cell and reprogram it to replicate.

Many scientists do not consider viruses to be living creatures,

but that does not make them any less dangerous.

This is an influenza virus, it is a master of disguise,

able to evade the body's immune system by constantly mutating.

This particular one is perhaps the worst spree killer in history,

the Spanish flu virus.

Between 1918 and 1920,

it is estimated to have killed 50 million people,

that's five times as many as the

industrialised slaughter of World War I.

And then, there's polio,

which attacks the nervous system, preying particularly on the young.

Iron lungs were needed because

severely affected polio victims cannot breathe unaided.

But there is one virus here that has killed more than any other,

and in the most grisly manner.

It has killed Japanese emperors, and European kings.

It wiped out 90% of the Aztecs and brought down their empire.

It was responsible for the deaths of at least 300 million people

in the 20th century alone.

It is, of course, smallpox.

Smallpox, throughout all of history,

going back at least 3,500 years,

has been the most serious pestilence that man has endured.

And the death rate was approximately 30%.

The smallpox virus is held in a level-four containment lab,

which is about as secure as it is possible to get.

And this is as far as I am allowed to go.

And granted, what a horrible disease it is,

it's about as close as I feel I really want to get.

Those unfortunate enough to catch this airborne disease,

were often hideously disfigured and suffered excruciating pain.

It develops first as little tiny pimples and

then, the individual would be covered with these pustular lesions,

particularly on the face, the arms and the legs,

but over the whole body.

It's in the inside of the mouth, on the tongue,

so the individual has trouble drinking,

and there's nothing really that you could do to ameliorate the pain.

There is no cure, and antibiotics are useless against it.

Smallpox is a monster.

But a monster that no longer exists in the wild.

Because smallpox is the first disease

in human history that we have managed to eradicate.

So how do you get rid of a monster that you cannot kill?

The answer, as with Pasteur and Koch, came from a rural setting.

It all began more than a century

before anyone knew that viruses even existed.

As a young man, 18th-century English doctor Edward Jenner

had heard a milkmaid bragging that she would never get smallpox,

because she had previously been infected by cowpox.

Cowpox is like a very mild form of smallpox.

Symptoms include pustules and blisters on the hands.

Now, Jenner was not the first doctor

to realise that cowpox could protect you against smallpox,

but he gets the glory, because he did the critical experiment.

One which these days would be regarded as so unethical

that he would certainly be struck off

and would probably end up in jail.

What Jenner did is

he got hold of an eight-year-old boy called James Phipps

and he deliberately infected James with some cowpox.

The boy developed a fever. Then what Jenner did is he got a scalpel,

and he made a couple of slashes in the boy's arm,

and then, he rubbed in puss from a smallpox victim.

Now, I have no idea what he told the boy or the boy's father,

but Jenner certainly knew that if the experiment went wrong,

the boy would go blind and might die screaming in agony.

Fortunately, the milkmaid had not lied.

Cowpox did provide immunity to smallpox

and, as far as we know, James lived happily ever after.

Jenner called his discovery vaccination,

after "vacca" - the cow,

and it relied on one simple principle.

The vaccine helps our body's immune system prepare for the

invasion of a particular infectious agent.

They give us, if you like, a preview of the invader,

allowing the immune system to adapt its defences.

A vaccine ensures that if the body is infected,

it is ready to make as many antibodies as we need.

It was a great addition to our medical armoury,

but more than that, Jenner had kindled the dream.

They knew that we might be able to transform the world

where we were entirely vulnerable to disease,

and change it into a world where we could fend them off,

where we mastered them, we could keep them at bay.

So Jenner would no doubt have been disappointed

that more than 150 years after his original experiment,

smallpox was still rampant,

killing and mutilating in more than 60 countries.

We were having, in the world, ten million cases a year,

with two million deaths.

So it was clearly a significant problem.

In 1966, the World Health Organisation set up a special unit.

Their mission, the complete eradication of smallpox

within ten years, or as they called it, Target Zero.

It was almost killed at birth.

It just barely passed, it just barely passed by two votes.

The team was headed by Donald Henderson, an epidemiologist.

Even he had his doubts.

In theory, I could say yes, you can stop the disease in

any number of countries.

We could do it worldwide.

But could you really stop a disease that was so widespread?

Could you really vaccinate every person on the planet?

Many eminent scientists thought this was impossible,

the practical problems were simply too great.

This would be another wonderful '60s utopian dream

that would end in failure.

People think you have to vaccinate everybody,

well, you don't.

Because I think we have to bear in mind

that smallpox has to go from person to person to person.

So the idea was to have a team go to the area where the cases were,

and vaccinate the people right around the cases.

And this would put a barrier in smallpox being able to spread.

Henderson's team travelled to some of the remotest places on Earth

to find cases of smallpox before they were able to spread.

NEWSREEL: 'Wanted - smallpox reports,

'200 shilling reward.

'News of the reward spreads quickly and it helps the searchers.'

To be successful, Henderson knew the

project would need to work closely with locals.

There was a tremendous camaraderie

that developed among all of the people.

We had, in all, nearly 800 people working at one time or another

from different countries, who dropped everything,

gave up family and worked in the field in the worst possible places.

I feel like one who was privileged

to be had of a...an army

who were, themselves, the real heroes.

By the mid 1970s, victory was tantalisingly close.

Smallpox now only existed in a few isolated pockets.

But the team also knew if

there was a major outbreak, then all their good work could be undone.

In October 1977, the team responded to reports of a smallpox case in the

Somalian port city of Merca.

When they arrived, they found a 23-year-old,

Ali Maalin, in the grips of the disease.

He was immediately isolated,

and everyone who had come in contact with him since developing smallpox

was tracked down and vaccinated.

They waited anxiously for news of other outbreaks.

But there were none.

Ali Maalin was the last

naturally-occurring smallpox victim in the world.

And he survived.

In just over ten years, and against extraordinary odds,

Henderson and his team had achieved Target Zero.

The eradication of smallpox has been hailed as a tremendous triumph.

Suddenly, there were awards and special recognitions and so forth.

It was a watershed event, in terms of an international programme,

which set us a goal, a time frame and succeeded.

I do think that the eradication of smallpox

is one of our greatest ever human achievements.

Far more significant than putting a man on the moon

or splitting the atom.

It is an absolute triumph of science and international cooperation.

But although the disease has been eradicated, the virus has not.

The CDC and Russia are the only two laboratories in the world

authorised by the World Health Organisation

to continue to hold the smallpox virus.

We do that so that if it were to come back, we would be fully prepared.

The fear is that a rogue state or terrorist

might somehow acquire the virus and use it as a biological weapon.

But Henderson is convinced we've already extracted everything useful

from the virus' DNA to fight any potential outbreak.

And the risks of us keeping something so lethal

are simply too great.

I've been very clear on this since 1995 - we should destroy the virus.

Regardless of the ongoing debate,

the eradication of smallpox was the catalyst for something much larger.

It opened up the potential for massive immunisation

using other vaccines which has resulted in,

what many call, the era of vaccines.

Prevention is the best buy, and vaccines are a powerful tool.

We're continuing to create new and better vaccines,

that can reduce illnesses,

whether it's hepatitis C or human papilloma virus,

or measles or polio.

In Victorian times, before vaccines were generally available,

infant mortality was horrific.

And a lot of that was due to infections,

which today we just struck off because babies are immunised.

Life expectancy has increased, infectious diseases are on the run,

but if we let down our guard, we'll be in trouble.

When George Washington died in 1799,

life expectancy in many Western cities was about 35 years.

It's now more than doubled.

Over the last 200 years,

a combination of astute observations,

dogged perseverance and sheer good luck

has seen science, firstly, identify the microbes that cause infections,

and then develop antibiotics and vaccines to fight them.

Bacteria and viruses are on the back foot.

For now.

It is unusual, very, very unusual now

for any of us to die when we're very young.

But talk of victory over disease is premature.

Our increasingly populated, mobile world means we are

more vulnerable to pandemics than ever before.

We do have a threat

of agents emerging from what is tropical rain forest

or haemorrhagic viruses,

like ebola and marburg from Africa,

which could spread and really be very destructive.

And there is a very real danger of a flu virus

mutating into something more lethal.

Pathogens are evolving, but they're

swapping genes between swine and bird and people,

so that we may have something as deadly as the 1918 pandemic.

While the rise of antibiotic resistant bacteria

risks turning our magic bullets into magic duds.

It is one of the biggest issues facing us in medicine today, I think.

Now, some people believe that, unchecked,

it could hurl us back into a medieval world,

where operations, childbirth and even minor injuries,

once again, lead to agonising death.

I do not believe that.

We know too much and we are learning more all the time.

In labs around the world,

scientists are sequencing pathogens,

tracking outbreaks and searching for new ways

to fight infectious disease.

I am optimistic.

I think that what we've learnt over the last 200 years

has put us in a good position

to combat whatever the microbes throw at us.

And in the next programme,

I'm going to find out how we turn

some of the world's most dangerous poisons

into some of our most effective medicines.

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