The Fantastical World of Hormones with Professor John Wass

There is a mysterious set of chemicals that flow through

every part of our bodies.

They can rule our lives and shape our destinies.

They turn children into adults, they govern our appetites

and they even affect our passions.

They are called hormones and they are fundamental to making us

who we are.

I'm John Wass,

a professor of endocrinology - that's the study of hormones.

Hormones have been my professional life for 40 years,

and they're absolutely fascinating.

To a greater or lesser extent, they control everything in your body.

How we unravelled the ways hormones work is one of the most

fascinating stories in the whole history of medicine.

COCK CROWS

It's a story that involves bizarre experiments,

and quite remarkable characters.

Along the way there have been some horrific wrong turns.

And some of the worst examples of opportunism and quackery.

Spermin Liquidim...

The hormones of two testicles.

HE GIGGLES

But there have been some inspired moments of genius,

and heart-warming tales of survival.

And here is a picture of Leonard Thompson,

and he should have been dead.

Today, hormones are at the cutting edge of medical science

and almost daily, we are learning that their effects are

more widespread than we ever imagined.

For me, this is a personal journey, as well,

it's a story I've wanted to tell all my life.

To share and instil my enthusiasm for this subject, which affects

each and every one of us, is the most wonderful opportunity.

Hormones are a crucial part of our biology and to understand them

is to better understand ourselves.

We've all heard of hormones,

but most of us don't think about them every day.

And for something so fundamental to our lives,

our understanding of hormones is remarkably recent.

The hormone system isn't an anatomical thing like the skeleton,

like the nervous system, like the cardiovascular system.

It's something which you don't see, so anatomically it's different.

I mean, it's easy being a cardiologist. They have

pain in the chest, there's something wrong with their heart

But with endocrine conditions it's completely different.

I think that's one of the reasons why

it's one of the last of the systems, if you like, to be discovered.

This endocrine or hormone system, though invisible, is

one of the most important factors in running and regulating our bodies.

The way we uncovered its secrets is a great medical detective story.

It's full of unexpected twists.

And I'm going to pick up the trail in the 1730s,

not with a great doctor and a brilliant experiment, as you might expect,

but in one of my favourite cities on the planet,

with a really surprising story.

In all my years as a doctor, and an opera lover,

I never dreamed I'd be standing on the stage

of the Theatre an der Wien, one of the world's great opera houses.

I want to play you and extraordinary sound.

PIANO MUSIC AND SOPRANO VOICE

Believe it or not this is the voice of a grown man, over six-feet tall.

Made in 1902, this is the only recording of a singer of this kind.

But arguably its greatest proponent lived in the 1730s.

He was a true musical star and his name was Farinelli.

This is the sound that Farinelli would have made.

Almost supernatural. Amazingly pure, gentle, sublime,

and yet forceful, because he was a fully grown man.

The reason for this extraordinary voice is that he was

a castrato - Farinelli was castrated before puberty,

in order to maintain the purity of that voice, which didn't break.

When a boy reaches puberty,

his voice can drop by as much as a whole octave...

# Ave Maria... #

..Making him unable to hit the high notes of the soprano range.

But, since Farinelli was castrated before this change could happen,

his voice remained high, even as he grew to full adulthood.

Amazingly, this shocking procedure continued

until the early 20th century.

And for many boys, castrated in the hope they would be the next

Farinelli, the effects were both dramatic and permanent.

It wasn't just his voice, there were other really important changes,

which you can see in this wonderful painting. You can see that

he had a straight hairline, like a woman, and didn't have the "V" shape

of a man. He's covered his lack of an Adam's apple with a silk scarf.

And castration even affected how much Farinelli grew.

He had an enormous chest, also his really long arms,

and the legs, too, will have been very long - they carry on growing.

And all of this because of castration.

Castrati serve as a very dramatic demonstration of what happens

when you remove the testicles, or testes, from humans.

And, of course,

people had observed the effects of castration on cattle for centuries.

But, amazingly, there was no scientific explanation

for why this happened, right into the 19th century.

So this is the big question that completely baffled people.

How on earth could the testes affect so many parts of the body

from your vocal cords to the length of your limbs?

Talk about a fall from grace -

I've gone from grand opera to chasing chickens.

But there is a good reason.

In 1849, a German physiologist called Arnold Berthold did

some extraordinary experiments on chickens which would reveal

the mechanism by which castration could affect the whole body.

Berthold was the Professor of Medicine in Goettingen,

that well-known university town in the middle of Germany,

and he also ran the Department of Zoology,

where he came across some birds called capons.

The capons' meat was incredibly tender,

a real delicacy in early 19th century Europe, and the reason

for this is, like a castrato, they'd had their testes removed.

Castration had a wide variety of effects on these birds.

Compared to regular cockerels, they became docile, meek even,

and lost all their sexual appetite.

But the main reason Berthold chose capons for his experiments was

because they had an obvious physical marker, which made them

easy to tell apart from cockerels, even at a glance.

This is Bernard,

a real bloke of a bird, I can tell you, he's itching to chase hens.

You can see his aptly named comb on the top of his head,

his wattle under his beak.

He's a full-blown male.

Capons were completely different - they had droopy combs

and droopy wattles.

BERNARD CROWS

Armed with this simple measure of masculinity,

Berthold began a series of experiments to see

if he could halt or even reverse the effects of castration.

What he wanted to do is to try

and reverse the changes that had gone on.

So he took the testes out of young cockerels,

then what he did was to transplant testes into cockerels,

not within their normal place in the body but in the abdomen,

and surprisingly, he found it would maintain their sexual activity,

their aggressive behaviour, and also maintain their wattles and combs.

With these birds,

Berthold now had a way to answer the completely crucial question,

how were the testicles able to affect distant parts of the body?

When Berthold came to do the autopsy on these birds, he found,

quite surprisingly, that the testes he'd put back into the abdomen

had redeveloped their own blood supply -

the blood vessels had grown round the testes.

So the key deduction was, that whatever effects were happening,

were happening through the blood.

And what Berthold showed, interestingly,

was there were obviously some chemicals

released from the testes that reacted at other parts of the body.

We now know that Berthold was seeing the action of the male sex hormone,

testosterone, which, released into the blood in huge amounts

at puberty, effectively turns boys into men.

No-one had any concept that chemicals alone could have

such a dramatic effect on the whole body.

But, strangely, his findings didn't have much impact

on the broader scientific community.

And Berthold himself didn't conduct any further research

into what he'd seen.

These were fabulously interesting observations,

and it's interesting that Berthold really didn't seem

to think very much as to why they had occurred.

So it was a huge, missed scientific opportunity

and it was going to be many decades before there was an explanation.

In the 20th century, scientists would rightly acknowledge

Berthold as the first to describe how the testicles work.

But, sadly, his contemporaries ignored his findings.

Instead, they made bizarre claims about the testicles.

And in particular, for men, at least,

they thought they might be the source of eternal youth.

Brown-Sequard's method...

HE LAUGHS

This extraordinary advertisement dates from the early 20th century

claims to have found the power to rejuvenate old men.

"Hormones of two testicles..."

HE LAUGHS

It's amazing. This is so funny.

The story of this ridiculous claim,

and its surprising consequences, begins in 1889

in one of the most august institutions in Europe...

..the Academy of Sciences in Paris.

At a very formal occasion, a serious audience came to hear

the announcement of one Charles Edouard Brown-Sequard.

At the age of 72, and at the end of a long

and distinguished career, as a scientist and a doctor,

he will have been familiar with the wonderful surroundings

in the Grand Salle de Sciences, the Academy of Sciences in Paris,

as a large number of eminent professors

gathered to hear him speak.

What Brown-Sequard announced was a truly unbelievable experiment.

He said he had prepared a concoction of the following three ingredients.

'Blood of the testicular veins, semen

'and juice extracted from a testicle, crushed immediately after

'it has been taken from a dog or a guinea-pig.'

The resulting blood and semen mixture,

he injected into himself.

This is what he told his astonished audience - that he

had more strength and stamina, his concentration powers had improved

and, as well, his mental energy was considerably better.

Apparently there was shocked silence in the audience.

But with an average age of 71, you can just imagine them thinking,

"Oh, my goodness, that would be good."

This had the potential to be

the elixir of life, and a possible breakthrough of the century.

The announcement sent the media into a complete frenzy

and with public demand for this kind of cure-all remedy

soaring across the globe, the papers were filled with articles

and advertisements about it alike.

Brown-Sequard was headline news throughout the whole world.

The press asked, was this a genuine elixir of life?

Of course, it wasn't!

But it was a call to arms, signalling the start

of a period of intense interest in the testicles and other related

organs, whose extracts people thought

could be used for medical purposes.

By tapping into a public thirst for miracle cures,

Brown-Sequard created a real phenomenon.

This was called "organotherapy,"

and involved the injection of various glands into people,

often with very little scientific evidence, to cure various illnesses.

But in the case of Brown-Sequard, no-one was able to repeat

his results experimentally, and the dramatic effects he had claimed on

his own body must have been down to nothing more than a placebo effect.

Unfortunately, it's unlikely that the watery extracts would

have contained any active substance at all.

So, Brown-Sequard's extract couldn't possibly have worked.

But the great interest it inspired in the effects of gland extracts

did have lasting consequences.

Throughout the next decade, the 1890s, there was a whole

series of genuine scientific breakthroughs,

ones that are a vital and extremely gratifying part of my job today.

So this was a woman I was treating who had an underactive thyroid

and one of her children sent me a card.

"Thank you for listening to my mum and giving her back."

And then her mother wrote, "I cannot thank you enough for giving me

"my daughter back, my grandchildren their mummy back

"and my son-in-law, his wife."

And all I had done was to give her thyroid hormone.

Lovely though it is to be thanked like this,

I really don't deserve it.

The real thanks should go to a pair of pioneering British doctors

from the 1890s. They were the first people to actually use

hormones to cure what, up until then,

was a debilitating and horrific illness.

This was the story of the first scintillating discovery

which resulted in a successful treatment in endocrinology

and it relates to the thyroid gland in the neck.

The treatment focused on disorders known as myxoedema and cretinism.

They're in fact similar conditions, which can leave sufferers physically

and mentally disabled.

They were relatively common even 100 years ago,

and cretinism even featured as a tick box on the Victorian census.

Fortunately, it is a disease that is completely manageable today

and that's because of the work started by this man.

Victor Horsley was born here in sunny old London,

into a family of artistic aristocrats.

But he had a huge social conscience

and was a forcible advocate of free health care for all.

But, for me, his most important work was on the thyroid.

I'm going to explain what he did

with the help of some props.

These are sheep's thyroids,

although when Horsley began his experiments he used monkeys.

And what Horsley did was to remove the thyroid from some monkeys

and showed that they developed changes of myxoedema

just like humans - their hair fell out and they became more lethargic.

With this proof, Horsley conclusively demonstrated

that myxoedema was caused by thyroid deficiency.

But beyond this,

he then went on to suggest the bold step of transplanting

tissue from sheep's thyroid,

just like these, into human patients.

Others across Europe took up the call and the practice

of transplanting sheep's thyroids into people had some success.

But this still wasn't a cure.

It was potentially dangerous surgery and the benefits were short-term.

So this was the problem - you can't carry on giving this

every seven days, and the effects only lasted for that time.

So the question was, how do we make that into a treatment?

It actually took the work of one of Horsley's students,

George Murray, to solve this problem in a highly unusual way.

Murray's solution was to cut the thyroid up into tiny, little bits,

put them in carbolic acid, stopper them overnight,

and then use a common-or-garden handkerchief.

And he used this handkerchief to strain these bits

and produce what he described as "pink thyroid juice".

This, in some ways, was a revolution.

It meant that there was a cheap, effective way of treating

these conditions of myxoedema and what resulted from cretinism.

And it was cheap,

because he obtained those thyroid glands from the abattoir.

The most famous patient, we only know her as Mrs S,

was 46 when Murray started treating her,

and she had obvious myxoedema with a swollen face and pale skin.

And Murray started giving her injections

of sheep's thyroid juice twice a week.

And within three months, there was a miraculous improvement in her

appearance - her skin was less pale and she'd actually improved

her energy such that Murray wrote in his notes that she could

do the housework much more easily.

Poor thing.

Mrs S lived to the ripe old age of 74,

which was a pretty good innings in 1890.

Thyroid hormones, in contrast to testosterone, last several

days in the blood, which is why these injections worked.

And this made them the first successful treatment in our story.

But really, Horsley and Murray had no idea what hormones were

Though successful, they were only observing

the effects of glands, with no understanding how they worked.

To get us closer to this, it would take the invention of a truly

ingenious device,

one which was actually able to show a hormone at work.

You could be forgiven for thinking that this was a Swiss

masterpiece watch from the turn of the century.

In fact, it's an amazing device invented by a physician

from Harrogate called George Oliver.

What this machine is called is an arteriometer

and it's a beautiful piece.

And what you do is, you simply put it on the wrist,

where the artery is

and you can measure the diameter of the artery on a gauge.

Oliver was looking to cure low blood pressure using extracts

from the adrenal gland - the glands that sit at the top of our kidneys.

'He had injected it into rabbits, all of whom had died as a result,

'but he was keen to test his extract on humans.'

And some people even say he used these on his son.

'Fortunately, his son survived, and gave Oliver the results he needed.'

What he showed was that the effects of adrenal extracts,

as measured on his arteriometer, caused a narrowing of the arteries,

and a resultant significant increase of the blood pressure.

What we now know is that Oliver was measuring the effect of adrenaline.

This chemical is released by a gland that sits on top of the kidneys.

It produces a signal to get the heart beating faster

and the blood flowing more quickly.

Being able to measure the affects of adrenaline

was an amazing breakthrough.

But the mechanism by which it and other hormones worked

was still a mystery.

It would be solved just a few years later...

..but at a terrible price.

Sadly, the crucial research to get us there would come out of one

of the most scandalous practices in the history of medicine.

This is the oldest operating theatre in England,

and in places like this, across Europe, women were undergoing

oophorectomy - that's the removal of both ovaries for such

"conditions" as hysteria, anorexia,

anxiety and even nymphomania.

And they thought that the ovaries were a source of all sorts

of mental disabilities, physical disabilities, and all

sorts of things, so they simply took out the ovaries of women.

And the reason they did this was

because of a huge misconception, all to do with the nervous system.

The general view was that the nervous system governed

all parts of the body, including the brain.

The glands were part of this system, and the ovaries, in particular,

were the nerve centres governing each and every woman.

Amazingly, it's estimated that 150,000 women across Europe

had this operation to try and cure them of their womanly ailments.

But far from this, they developed fresh complications.

And of course if you take out the ovaries of women, it causes early

menopausal symptoms, so in fact women were back to square one on it.

Doctors wanted to know why oophorectomies

were causing this problem.

While trying to find a solution, one man conducted experiments

that would turn accepted science on its head.

Josef Halban undid the idea that glands communicated through

nerves, and in doing so, he finally gave us

the first clear picture of how the hormone system works.

What Halban did was he took out the ovaries and bits of uterus

and a little bit of the womb,

and he transplanted these under the skin of young guinea pigs.

And what he showed is that the ovaries, and the uterus,

and the womb, showed changes that you would expect to be in

if it was in situ in the animal from which it came from.

This proved that the ovaries worked if moved from their original site.

More importantly, they carried on working,

even when there were no nerves connecting them

to the rest of the body.

Halban's discovery effectively put an end to oophorectomies

and it had a huge implication for story of hormones as well.

By this means, he showed that the ovaries weren't controlling things

by nerves, instead by internal secretions, chemical messengers,

which move around the body in the blood, affecting distant parts.

These secretions, put together,

made a new system - the endocrine system.

The definition of this new system was the final

piece of the jigsaw for hormones.

And with the turn of the 20th century, science had finally

caught up with the forgotten observations Berthold had made.

His work on cockerels, Horsley and Murray's experiments with thyroid

glands, George Oliver's discovery of adrenaline, and now Halban.

All of it came together to give us

a modern understanding of a separate system of internal secretions

constantly at work within our bodies.

All that was now needed was to give these secretions a name.

The story goes, that at a University dinner in Cambridge,

Ernest Starling, a leading physiologist of the day,

coined the term that we have all come to use.

As Starling sat talking with a colleague,

they both struggled to find a name for these secretions that

could pass to another part of the body and stimulate it directly.

A scholar of Ancient Greek just happened to pass by and

so they asked him.

someone said, "Well , they ought to call it something like hormao,"

which is the Greek word for "I excite" or "stir up".

And, interestingly, Starling then gave

a lecture at the Croonian Society,

and suddenly used the word "hormone".

Noone had heard it before, and that was it.

The name stuck and today we've all heard of hormones.

But you may not realise just how fundamental they are.

Every form of life that has more than one cell - every plant,

every animal, from an earthworm to a killer whale uses hormones.

There are more than 80 known hormones in humans alone,

and they all have vastly different roles.

If you're feeling stressed,

that's one of the stress hormones, cortisol, at work.

If you're preparing for exercise, adrenaline will kick in,

that well known "fight-or-flight" hormone.

Hormones even have a hand in the bonding process.

That one's oxytocin.

But what are hormones?

Well, there are different types - amines, peptides and steroids,

and every single hormone has a different molecular structure.

But what unites them is how they work.

Each hormone is aimed at a particular target cell.

Strange as it may be, let's imagine I'm a hormone,

heading for my target.

Each hormone flows through the bloodstream,

passing over billions of cells.

But they will only have their desired effect when they reach

the right one, a cell that matches their specific chemical structure.

You see, hormones only work at specific cells.

Anywhere else, it's like trying to unlock a door with the wrong key.

'OK, wrong cell - let's try that again.'

At these specific target cells, the key fits perfectly

and the hormone effectively unlocks the cell to get it working.

Once the hormone acts on its target cell,

it can change the way it behaves to make it perform a specific task.

For example, when adrenaline reaches the heart, it makes it beat faster.

Each hormone has its own unique role.

Hormones have many different actions

and many different timescales of action.

So adrenaline has an effect on the heart for only a few

minutes, whereas oestrogen, secreted every day,

has effects which last for years.

Building up over long timescales like this,

some hormones can have dramatic effects on our body.

As one of my former patients can help to demonstrate.

At seven-foot-six,

this is Chris Greener, one of Britain's tallest men.

And here he is with our film's director, James,

who's a good five-foot-nine.

Chris leads a healthy, if unusual life.

When people say to me, "What's the problems about being tall?"

I say, "Oh, well, getting clothes. I have to have everything

"made-to-measure."

I've had this problem for, well, the best part of 50 years.

When I left primary school, I was taller than most of the teachers.

I just thought I would stop growing, but I didn't.

HE LAUGHS

Chris's condition, called acromegalic gigantism,

we now know is caused by over-production of growth hormone.

Which meant he kept growing,

and growing and growing well into his 20s.

When I started work, I was six-foot-seven.

when I was named tallest man, I was about seven-foot-five.

So I grew about ten inches in seven years.

Some of those years, I was probably growing in excess of two

inches a year.

It was by studying people like Chris that the mysterious role

hormones play in growth was unravelled.

The story starts in the 1780s, with a man similar in stature to Chris.

When Irishman Charles Byrne came to London to earn

a living as a human curiosity, he quickly attracted the

attention of a notorious scientist and collector called John Hunter.

Going against Byrne's dying wish to be buried at sea,

Hunter stole his body and displayed the skeleton in a museum.

And, as unethical as this was,

it did leave scientists an invaluable clue.

More than a century later, in 1909, the brilliant neurosurgeon,

Harvey Cushing, tried to explain why Byrne had grown so tall.

He used the skull to suggest that the cause might lie within

a tiny gland that's hidden at the base of the brain.

It's called the pituitary and it's incredibly

difficult to find, as pathologist Dr Suzie Lishman explains.

This is a human brain,

and you can see that it is an amazingly complex

and rich network of nerves controlling all of our movement,

our sensations, and our higher function.

So where does the pituitary gland fit into all this?

Well, it's not quite as easy to see,

and the only clue we've really got is this very short stalk.

This is the pituitary stalk and this is where the pituitary gland

is attached. We had to remove it when we removed the brain.

Now, if we have a look at the pituitary,

here it is - a tiny organ, around the size of a baked bean,

that sits on that stalk at the base of the brain, and I think

you can just see the stalk, that attaches it to the brain.

Back in the 1900s,

Cushing didn't really fully understand what the pituitary did,

but he was convinced it was important because of where it was.

And if we look in the base of the skull,

we can see where the pituitary nestles,

in this area called the pituitary fossa.

So it's very carefully protected by a ring of bone to make

sure that it doesn't get damaged.

The protective bone layer convinced Cushing

of the pituitary's importance and that here lay the explanation

of Charles Byrne's unusual height.

And that's what's so interesting when Harvey Cushing

examined the skull of Charles Byrne.

Instead of having this small, bean-sized area, there was

a much, much bigger hole and that's because the bone had been

eroded, and Cushing deduced that that was because he had

a pituitary adenoma, or tumour, that had grown, forcing the bone away.

Cushing deduced, correctly as it turns out,

that Byrne's height was due to this tumour on the pituitary,

causing it to overproduce a hormone that tells our bodies to grow.

A similar pituitary tumour had caused Chris Greener's height.

As with the Irish giant,

the tumour caused the pituitary to carry on pumping excessive

quantities of growth hormone long past his teenage years.

They put it on the machine and pressed the button

and the needle went "bing", off the end.

They reckoned I had over 200 growth hormones per unit of blood,

when the average is about 15, plus or minus a couple.

Charles Byrne died at the age of 22, with his tumour still untreated.

But in Chris's case, we were able to destroy his tumour with radiotherapy

and he stopped growing, and he's still going strong at the age of 70.

Conditions like Chris' are fascinating.

Though incredibly rare,

they serve to emphasise just how important hormones are.

And, as we shall see, the next breakthrough in our understanding

of hormones quite literally transformed the lives of millions.

This is a vial of human insulin. It's a hormone.

Probably the best-known hormone of them all.

Without it, you develop diabetes and although that is treatable now,

before the discovery of insulin, diabetes was a death sentence.

For children who don't make the hormone, insulin,

sugar that would otherwise be absorbed as energy,

passed straight through the body into their urine.

This is why the disease is called diabetes.

The most common form, diabetes mellitus, literally means

"a sweet fountain", because the urine of a sufferer tastes sweet.

Without the ability to store this vital energy, the child

slowly wasted away to nothing and never survived beyond their teens.

It was incredibly difficult to find a cure to diabetes,

even though there was evidence that one organ in particular,

the pancreas, might be at the root of it.

In the late 19th century, a couple of German physiologists

and clinicians removed the pancreas from dogs,

and showed that they got diabetes.

Now, this led the way to identifying the pancreas as the source

of raising blood sugar levels, that is, becoming diabetic.

This is a pig's pancreas and it's about the same size

and shape as a human pancreas, which is

located in the upper part of the tummy, at the back.

And it's an amazing organ because it has two main functions.

One is to produce digestive juices,

which enter the stomach through the pancreatic duct, there,

and the other is to produce insulin, which controls sugar levels.

This presented a problem for anybody who wanted to use

the pancreas as a potential cure for diabetes.

The trouble with the pancreas is that, actually, most

of the pancreas is made up of cells that secrete digestive enzymes.

So if you'd have just mashed up the pancreas,

there would've been virtually no insulin in it.

All it would've been would've been, in fact, digestive juices.

So, who was the genius to crack this problem

and earn what was the first Nobel Prize in Endocrinology?

Frederick Banting was, in fact, the unlikeliest of medical pioneers.

He certainly didn't hit on his revolutionary cure for diabetes

while working in a well-funded lab.

Rather, he was a failing GP in Ontario in Canada.

He was heavily in debt

and would subsidise his income by giving lectures to medical students.

And yet, he was responsible for one of the most sensational

and dramatic discoveries in the whole of endocrinology.

During his research for one of these lectures,

he just happened to come across an article in the little-known

publication, Surgery, Gynaecology and Obstetrics.

This referred to the possibility of stopping the digestive

function of the pancreas, effectively killing off the enzymes,

and just leaving the hormone-producing cells

to do their work.

He spent the day slogging over his notes,

thinking how the body controls sugar and, in particular,

how the pancreas deals with it.

He went to bed with these thoughts still running through his mind,

and woke, quite suddenly, with a surprising revelation.

And this was Frederick Banting's "eureka" moment.

And these are the words of a note he wrote in the middle

of the night. He said, "Diabetus" - spelled wrong, he was

an appalling speller, apparently,

but it was the middle of the night...

"Ligate the pancreatic ducts of dogs.

"Keep dogs alive till the acini degenerate leaving the islets.

"Try to isolate the internal secretion of these to relieve

"glycosurea".

You need to be a doctor to understand that,

but this was the first steps in the cure to diabetes.

He suddenly thought, "If I tie off the duct that produces all

"these digestive enzymes from the pancreas, perhaps they might

"degenerate and I could therefore

"isolate the few cells, or islets,

"that produce insulin, and thereby produce an insulin supplement."

What Banting did was to operate on dogs

and surgically tie off the pancreatic duct, there.

He kept them alive for six weeks, and at the end of that time

the digestive enzyme cells had died, and he was essentially left

with a pancreas that was just producing insulin.

Amazingly, when trialled on animals, extract from this dog

pancreas proved Banting's theory was right, and by January 1922,

he was ready see whether the same extract would work on humans.

Leonard Thompson had been a diabetic from a very early age.

And in 1921, when he was 14,

he was admitted to Toronto General Hospital, days away from death.

He looked so thin, some people thought he was a famine victim.

He was pale, his hair was falling out,

and he smelled of acetone, characteristic of diabetes.

And it was that stage that he

and his father agreed to have Banting's new experimental treatment

containing insulin, of what was described as "thick, brown muck."

After a little refinement, this so-called "muck",

still made from dog's pancreas,

gave Thompson a whole new lease of life.

And here's a picture of Leonard Thompson.

This is after he started treatment with insulin

and he should have been dead, but happily,

he was first patient to be successfully treated and it's

wonderful because I've never seen a picture of Leonard Thompson before.

Now produced synthetically, insulin has gone on to save

the lives of millions - by any measure, a complete medical triumph.

In the 1920s, however, it opened the floodgates to a new wave

of hormone research, with others hoping to find more miracle cures.

Sadly, as we have seen before,

this quest can have very unwelcome consequences.

After this great success, we go from the sublime to the "cor, blimey".

Because endocrine science, for a bit, went seriously off track.

The days of Brown-Sequard may have been long behind us,

but the hope for a secret to eternal youth remained.

And with the miraculous survival of Leonard Thompson,

and other diabetics like him,

the idea grew that if replacing missing hormones could cure

the sick, surely increasing normal levels could enhance the healthy.

Cue one of the most bizarre fads in medical history.

All across Europe, and indeed the world, men began to subject

themselves to an operation which was extremely perverse.

What they wanted to do was to recapture their youth.

This is the Prater in Vienna - the oldest amusement park in the world.

Surprisingly, in the early 20th century, it was the site

of a laboratory which carried out quite remarkable experiments.

The Biological Research Institute, on the grounds of this park,

also went by the nickname of "the vivarium",

and it was here that physiologist Eugen Steinach developed

a procedure which he claimed could reverse the ageing process.

This lab was particularly interested in changing the body's

natural processes.

Steinach proposed a very similar technique to the one Banting

had used to obtain insulin in the pancreas, tying off the duct

from a gland to isolate one particular hormone within.

This time, however, he wanted to isolate the male hormone

testosterone and, for that, he had a very different organ in mind.

Steinach's procedure was to tie off the tube carrying the sperm -

in modern parlance, a vasectomy.

What he thought would happen was that this would create more

room for the hormone-producing cells in the testes,

and this would give his patients more vigour.

Hard as it is to believe, "the Steinach" was a sensation,

with people flocking to have it done on themselves,

including some rather high-profile patients.

Among them was the famous poet William Butler Yeats.

At 69, Yeats was in poor health, and really quite depressed,

and he had writer's block.

But, after the procedure,

he noticed a huge increase in his creative powers,

as well as his sexual desire.

Interestingly, some people think Yeats wrote

some of his best poetry after the procedure.

'A young man in the dark am I, But a wild old man in the light,

'Then, said she to that wild old man, His stout stick under his hand

'Love to give, or to withhold, is not at my command'

And it wasn't just his poetry.

A few months after the Steinach, Yeats took up with an actress

who, at 27, was 42 years younger than him.

Had Steinach stumbled on the secret of eternal youth?

Well, of course he hadn't.

And just as with Brown-Sequard, there was

no way to reproduce the results he'd claimed.

We now know that there is no scientific rationale,

and that it was another scientific blind alley.

Endocrinology had come a long way by the time we reach Steinach,

but his procedure failed because his understanding of how hormones

work was far too simplistic.

Steinach thought that the more testosterone there was

circulating around the body, the more invigorated you became.

But the problem was, it wasn't that simple.

First, Steinach was wrong to think that tying off the sperm

ducts caused an increase of the male sex hormone testosterone.

But, more crucially, even if he could have raised its levels,

he completely misjudged what would happen.

There's only one part of the endocrine system

he hadn't understood and that's the most important part of all.

Steinach had no idea how hormones are regulated.

But the publicity around his claims spurred on a huge

amount of research,

and out of this came an explanation of where he'd gone wrong.

And, more than this, it gave a new understanding of a key

role of a tiny gland we've met before - the pituitary.

As well as producing growth hormone,

the pituitary has the crucial job of ensuring that the

levels of many hormones never get too high or too low.

And that's why Steinach's technique couldn't possible have worked.

Even if you overload the endocrine system with testosterone,

normally the pituitary will step in to bring the levels

back down again to normal.

In many ways, the pituitary works just like a household thermostat.

It can sense if hormone levels have gone wrong

and send messages to some of the major glands, getting them

to produce more or less hormone as needed.

The discovery of this aspect of the pituitary was a real

milestone in my field.

Even when I was a medical student in the '60s,

this tiny gland was still considered the lynchpin to hormone regulation.

But what I love about this story is it never stands still.

And even in the last few years, research has uncovered an entirely

new system of regulation, which has led us to broaden our views.

In fact, this new system is challenging our perceptions of not

only how we control hormones but, indeed, how hormones control us.

Professor Sadaf Farooqi has been working at the cutting edge

of hormone research for more than a decade.

She and her team have been studying the role of hormones in obesity.

And in this condition, hormones work in a much more surprising way

than we ever imagined.

So the first real breakthrough emerged with

the discovery of a completely new hormone called leptin,

which was first found in mice which were severely obese.

And this really paved the way for finding out an entirely new

system for how weight is regulated.

And this system depends on the hormone leptin, which is

actually made by our fat.

It was a discovery that was entirely unprecedented - a hormone

produced not by a gland, but by cells which no-one thought

had any part in the endocrine system.

And this is something we had not realised before.

We didn't know that fat could make hormones. We knew that fat

is there to store extra calories, but this was a really important

discovery because we learnt that fat could make a hormone that circulated

in the bloodstream and acted on the brain to control our weight.

Incredibly, with this hormone, our fat cells themselves can control

how much we eat by setting up their own feedback loop with the brain.

It works like this.

Leptin is constantly being produced by our fat cells, and the more

fat stores we have in general, the more leptin flows in the blood.

This essentially tells our brain that we've eaten enough

and we lose our appetite.

But where Sadaf's work comes in is when this system doesn't work

properly, and, for some reason, the fat cells don't make leptin.

Sadaf is still working to understand all the reasons behind how

this can happen, but by figuring out one cause in particular,

she has already made a fantastic discovery.

Remarkably, a patient's inability to produce leptin can,

in some cases, come down to their genes.

A key part of how we discovered the role of the hormone leptin

was using genetics, and we were able to look at the DNA of patients

and find that they had a mutation or a gene defect that was

disrupting the hormone leptin.

And this was the cause of their weight problem.

In the rare case that someone has this faulty gene, they will be

unable to control their appetite and so will eat more than their

body needs and this will inevitably mean that they become obese.

Up until that time, most people thought that actually

your tendency to gain weight was purely down to self-control.

It was purely down to the food you eat and the exercise you do,

and there wasn't really any biology involved.

Actually what we showed through the discovery of leptin

and its lacking in patients is that, in fact, genes can play

an important role in controlling our weight, and they do

so by affecting our appetite,

and leptin is a key regulator of appetite.

It's an incredible discovery - that hormones are a key

factor in our ability to maintain a healthy weight.

And the fact that even a person's appetite can be marshalled

by a hormone has given people new hope in the battle against obesity.

That really meant that we can find treatments for those patients.

And we were able to give them leptin back,

and we did that by giving them injections, which they take

twice a day, and, thankfully, it's worked incredibly well and now they

live entirely normal lives, they are a normal weight, and many of

the other health problems that they suffered with have been corrected.

With the simple introduction of leptin, Sadaf has been able

to effectively cure obesity in those patients who would

otherwise have no control over their weight.

It's a striking example of the power of hormones.

And, alongside other recent breakthroughs,

it suggests that we are on the verge of discovering a whole range

of new hormones with potentially breathtaking capabilities.

Well, it's fascinating, really,

because we've come from understanding

what the classical endocrine glands were, that is

from Brown-Sequard and everyone mashing up a few glands,

to realising that, actually, most of our body now produces hormones,

and I think in the future the discovery of new

hormones is going to be absolutely vast.

Work like Sadaf's forces us to reassess

whether what we do is down to free will or simply our hormones.

And it's a heady thought to think that, one day, we might harness the

power of these chemicals to control almost every aspect of our biology.

But there are lessons to be learned from the history of hormones.

Stories like oophorectomies and the search for eternal youth remind us

that a little bit of knowledge is a decidedly dangerous thing.

Even now, we mustn't assume that we have all the answers.

As soon as we think we understand hormones completely,

a new discovery will come along and prove just how little we know.

It's extraordinary that the study of hormones is only just over

100 years old.

There have been amazing discoveries

and yet it's a science that is in its infancy.

And, for me, the ongoing fascination is that it's going to be

many years before hormones reveal all their secrets.