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00:00There's a mysterious set of chemicals that flow through every part of our bodies.
00:19They can rule our lives and shape our destinies.
00:25They turn children into adults, they govern our appetites, and they even affect our passions.
00:36They are called hormones, and they are fundamental to making us who we are.
00:45I'm John Woss, a professor of endocrinology, that's the study of hormones.
00:52Hormones have been my professional life for 40 years, and they're absolutely fascinating.
00:58To a greater or lesser extent, they control everything in your body.
01:05How we unraveled the way hormones work is one of the most fascinating stories in the
01:10whole history of medicine.
01:16It's a story that involves bizarre experiments and quite remarkable characters.
01:23Along the way, there have been some horrific wrong turns, and some of the worst examples
01:31of opportunism and quackery.
01:33That's the sperm in liquid of hormones of two testicles.
01:42But there have been some inspired moments of genius, and heartwarming tales of survival.
01:49And here's a picture of Leonard Thompson, and he should have been dead.
01:57Today, hormones are at the cutting edge of medical science, and almost daily, we're learning
02:04that their effects are more widespread than we ever imagined.
02:10For me, this is a personal journey as well.
02:14It's a story I've wanted to tell all my life.
02:18To share and instill my enthusiasm for this subject, which affects each and every one
02:23of us, is the most wonderful opportunity.
02:28Hormones are a crucial part of our biology, and to understand them is to better understand
02:35ourselves.
02:40We've all heard of hormones, but most of us don't think about them every day.
02:55And for something so fundamental to our lives, our understanding of hormones is remarkably
03:01recent.
03:02The hormone system isn't an anatomical thing, like the skeleton, like the nervous system,
03:08like the cardiovascular system.
03:10It's something which you don't see, so anatomically, it's different.
03:14I mean, it's easy being a cardiologist, they have pain in the chest, there's something
03:17wrong with our heart.
03:19But with endocrine conditions, it's completely different.
03:22And I think that's one of the reasons why it's one of the last of the systems, if you
03:26like, to be discovered.
03:30This endocrine or hormone system, though invisible, is one of the most important factors in running
03:37and regulating our bodies.
03:41The way we uncovered its secrets is a great medical detective story.
03:47It's full of unexpected twists.
03:49And I'm going to pick up the trail in the 1730s, not with a great doctor and a brilliant
03:57experiment, as you might expect, but in one of my favourite cities on the planet, with
04:05a really surprising story.
04:11In all my years as a doctor and an opera lover, I never dreamed I'd be standing on the stage
04:17of the Theater an der Wien, one of the world's great opera houses.
04:23I want to play you an extraordinary sound.
04:28Believe it or not, this is the voice of a grown man, over six foot tall.
04:35Created in 1902, this is the only recording of a singer of this kind.
04:44But arguably, its greatest proponent lived in the 1730s.
04:50He was a true musical star, and his name was Farinelli.
04:56This is the sound that Farinelli would have made.
05:10Almost supernatural, amazingly pure, gentle, sublime, and yet forceful, because he was
05:18a fully grown man.
05:22The reason for this extraordinary voice is that he was a castrato.
05:28Farinelli was castrated before puberty, in order to maintain the purity of that voice,
05:34which didn't break.
05:44When a boy reaches puberty, his voice can drop by as much as a whole octave,
05:55making him unable to hit the high notes of the soprano range.
06:05But since Farinelli was castrated before this change could happen, his voice remained high,
06:12even as he grew to full adulthood.
06:17Amazingly, this shocking procedure continued into the early 20th century.
06:24And for many boys, castrated in the hope that they would be the next Farinelli,
06:29the effects were both dramatic and permanent.
06:34It wasn't just his voice. There were other really important changes, which you can see
06:40in this wonderful painting. You can see that he had a straight hairline, like a woman,
06:46and didn't have the V-shape of a man. He's covered his lack of an Adam's apple with a silk scarf.
06:54And castration even affected how much Farinelli grew.
06:59He had an enormous chest, also his really long arms, and the legs, too, will have been very long.
07:05Farinelli may carry on growing, and all of this because of castration.
07:12Castrati serve as a very dramatic demonstration of what happens
07:16when you remove the testicles, or testes, from humans.
07:22And, of course, people had observed the effects of castration on cattle for centuries.
07:29But, amazingly, there was no scientific explanation for why this happened right into the 19th century.
07:38So this is the big question that completely baffled people.
07:42How on earth could the testes affect so many parts of the body,
07:47from your vocal cords to the length of your limbs?
07:50Talk about a fall from grace.
07:53I've gone from grand opera to chasing chickens.
08:00But there's a good reason.
08:07In 1849, a German physiologist called Arnold Berthold
08:12did some extensive research on the effects of castration.
08:16The German physiologist called Arnold Berthold
08:19did some extraordinary experiments on chickens,
08:23which would reveal the mechanism by which castration could affect the whole body.
08:36Berthold was a professor of medicine in Göttingen,
08:39that well-known university town in the middle of Germany.
08:43And he also ran the department of zoology,
08:46where he came across some birds called capons.
08:50The capons' meat was incredibly tender, a real delicacy in early 19th century Europe.
08:56And the reason for this is, like a castrato, they'd had their testes removed.
09:03Castration had a wide variety of effects on these birds.
09:07Compared to regular cockerels, they became docile, meek even,
09:13and lost all their sexual appetite.
09:17But the main reason Berthold chose capons for his experiments
09:21was because they had an obvious physical marker,
09:24which made them easy to tell apart from cockerels, even at a glance.
09:32This is Bernard, a real bloke of a bird.
09:36And I can tell you he's itching to chase hens.
09:39You can see his aptly named comb on the top of his head,
09:43his wattle under his beak.
09:45He's a full-blown male.
09:48Capons were completely different.
09:50They had droopy combs and droopy wattles.
09:57Armed with this simple measure of masculinity,
10:00Berthold began a series of experiments
10:02to see if he could halt or even reverse the effects of castration.
10:06What he wanted to do was try and reverse the changes that had gone on.
10:10So he took the testes out of young cockerels.
10:14Then what he did was to transplant testes into cockerels,
10:20not within their normal place in the body, but in the abdomen.
10:24And surprisingly, he found it would maintain their sexual activity,
10:31their aggressive behaviour, and also maintain their wattles and combs.
10:36With these birds, Berthold now had a way to answer the completely crucial question,
10:42how were the testicles able to affect distant parts of the body?
10:49When Berthold came to do the autopsy on these birds,
10:53he found, quite surprisingly, that the testes that he'd put back into the abdomen
10:59had developed their own blood supply.
11:01The blood vessels had grown round the testes.
11:04So the key deduction was that whatever effects were happening,
11:08were happening through the blood.
11:14And what Berthold showed, interestingly,
11:18were there were obviously some chemicals released from the testes
11:23that reacted at other parts of the body.
11:27We now know that Berthold was seeing the action of the male sex hormone testosterone,
11:32which, released into the blood in huge amounts at puberty,
11:37effectively turns boys into men.
11:41No one had any concept that chemicals alone could have such a dramatic effect on the whole body.
11:50But strangely, his findings didn't have much impact on the broader scientific community.
11:56And Berthold himself didn't conduct any further research into what he'd seen.
12:04These were fabulously interesting observations.
12:06And it's interesting that Berthold really didn't seem to think very much as to why they had occurred.
12:12So it was a huge missed scientific opportunity.
12:17And it was going to be many decades before there was an explanation.
12:21In the 20th century, scientists would rightly acknowledge Berthold
12:25as the first to describe how the testicles work.
12:29But sadly, his contemporaries ignored his findings.
12:33Instead, they made bizarre claims about the testicles.
12:37And in particular, for men at least,
12:40they thought they might be the source of eternal youth.
12:45Brown-Seckhard's method.
12:49This extraordinary advertisement from the early 20th century
12:53claims to have found the power to rejuvenate old men.
12:58Hormones of two testicles.
13:01This is so funny.
13:08The story of this ridiculous claim and its surprising consequences
13:13begins in 1889 in one of the most august institutions in Europe.
13:20The Academy of Sciences in Paris.
13:24At a very formal occasion, a serious audience came to hear the announcement
13:29of one Charles Edward Brown-Seckhard.
13:34At the age of 72, and at the end of a long and distinguished career
13:38as a scientist and a doctor,
13:41he will have been familiar with the wonderful surroundings
13:44in the Grande Salle de Sciences, the Academy of Sciences in Paris,
13:49as a large number of eminent professors gathered to hear him speak.
13:54What Brown-Seckhard announced was a truly unbelievable experience.
13:59What Brown-Seckhard announced was a truly unbelievable experiment.
14:05He said he had prepared a concoction of the following three ingredients.
14:11Blood of the testicular veins, semen, and juice extracted from a testicle
14:17crushed immediately after it has been taken from a dog or a guinea pig.
14:23The resulting blood and semen mixture he injected into himself.
14:34This is what he told his astonished audience,
14:37that he'd more strength and stamina, his concentration powers had improved,
14:42and as well, his mental energy was considerably better.
14:47Apparently, there was shocked silence in the audience.
14:50But with an average age of 71, you can just imagine them thinking,
14:53oh my goodness, that would be good.
14:56This had the potential to be the elixir of life
15:00and a possible breakthrough of the century.
15:05The announcement sent the media into a complete frenzy.
15:09And with the public demand for this kind of cure-all remedy soaring across the globe,
15:15the papers were filled with articles and advertisements about it alike.
15:20Brown Ciccard was headline news throughout the whole world.
15:24The press asked, was this a genuine elixir of life?
15:29Of course it wasn't.
15:32But it was a call to arms, signaling the start of a period of intense interest in the testicles
15:38and other related organs, whose extract people thought could be used for medical purposes.
15:45By tapping into the public thirst for miracle cures,
15:48Brown Ciccard created a real phenomenon.
15:52This was called organotherapy,
15:55and involved the injection of various glands into people,
15:59often with very little scientific evidence, to cure various illnesses.
16:05But in the case of Brown Ciccard, no one was able to repeat his results experimentally,
16:10and the dramatic effects he had claimed on his own body
16:13must have been down to nothing more than a placebo effect.
16:18Unfortunately, it's unlikely that the watery extracts would have contained any active substance at all.
16:26So, Brown Ciccard's extract couldn't possibly have worked.
16:31But the great interest it inspired in the effects of gland extracts did have lasting consequences.
16:38Throughout the next decade, the 1890s,
16:42there was a whole series of genuine scientific breakthroughs,
16:46ones that are a vital and extremely gratifying part of my job today.
16:54So this was a woman I was treating who had an underactive thyroid,
16:58and one of her children sent me a card,
17:00thank you for listening to my mum and giving her back.
17:03And then her mother wrote,
17:05I cannot thank you enough for giving me my daughter back,
17:08my grandchildren, their mummy back,
17:10and my son-in-law, his wife.
17:13And all I'd done was to give her thyroid hormone.
17:16Lovely though it is to be thanked like this, I really don't deserve it.
17:21The real thanks should go to a pair of pioneering British doctors from the 1890s.
17:27They were the first people to actually use hormones
17:30to cure up until then what was a debilitating and horrific illness.
17:36This was the story of the first scintillating discovery
17:41which resulted in a successful treatment in endocrinology.
17:44And it relates to the thyroid gland in the neck.
17:50The treatment focused on disorders known as myxedema and cretinism.
17:55They're in fact similar conditions
17:57which can leave sufferers physically and mentally disabled.
18:02They were relatively common even 100 years ago,
18:06and cretinism even featured as a tick box on the Victorian census.
18:14Fortunately, it is a disease that is completely manageable today.
18:19And that's because of the work started by this man.
18:24Victor Horsley was born here in sunny old London
18:28into a family of artistic aristocrats.
18:31But he had a huge social conscience
18:35and was a forcible advocate of free healthcare for all.
18:44But for me, his most important work was on the thyroid.
18:51I'm going to explain what he did with the help of some props.
18:58These are sheep's thyroids,
19:00although when Horsley began his experiments, he used monkeys.
19:05And what Horsley did was to remove the thyroid from some monkeys
19:08and showed that they developed changes of myxedema just like humans.
19:13Their hair fell out and they became more lethargic.
19:16With this proof, Horsley conclusively demonstrated
19:20that myxedema was caused by thyroid deficiency.
19:25But beyond this, he then went on to suggest the bold step
19:29of transplanting tissue from sheep's thyroid,
19:32just like these, into human patients.
19:38Others across Europe took up the call
19:41and the practice of transplanting sheep's thyroids into people
19:44had some success.
19:47But this still wasn't a cure.
19:49It was potentially dangerous surgery
19:52and the benefits were short-term.
19:56So this was the problem.
19:58You can't carry on giving this every seven days
20:01and the effects only lasted for that time.
20:04So the question was, how do we make that into a treatment?
20:09It actually took the work of one of Horsley's students, George Murray,
20:14to solve this problem in a highly unusual way.
20:19Murray's solution was to cut the thyroid up into tiny little bits,
20:24put them in carbolic acid,
20:27stopper them overnight,
20:30and then use a common or garden handkerchief.
20:35And he used this handkerchief to strain these bits
20:38and produce what he described as pink thyroid juice.
20:46This, in some ways, was a revolution.
20:49It meant that there was a cheap, effective way of treating
20:53these conditions of mixed haemostasis
20:55and what resulted from crestinism.
20:58And it was cheap because he obtained
21:00these thyroid glands from the abattoir.
21:03The most famous patient, we only know her as Mrs S,
21:07was 46 when Murray started treating her
21:09and she had obvious myxedema with a swollen face and pale skin.
21:14And Murray started giving her injections
21:16of sheep's thyroid juice twice a week.
21:20And within three months there was a miraculous improvement in her appearance.
21:24Her skin was less pale and she'd actually improved her energy
21:28such that Murray wrote in his notes
21:30that she could do the housework much more easily.
21:34Poor thing.
21:35Mrs S lived to the ripe old age of 74,
21:38which was a pretty good innings in 1890.
21:43Thyroid hormones, in contrast to testosterone,
21:46last several days in the blood,
21:48which is why these injections worked.
21:51And this made them the first successful treatment in our story.
21:56But really, Horsley and Murray had no idea what hormones were.
22:01Though successful, they were only observing the effects of glands
22:05with no understanding how they worked.
22:10To get us closer to this,
22:12it would take the invention of a truly ingenious device.
22:16One which was actually able to show a hormone at work.
22:26You could be forgiven for thinking
22:29that this was a Swiss masterpiece watch from the turn of the century.
22:34In fact, it's an amazing device
22:37invented by a physician from Harrogate called George Oliver.
22:41What this machine is called is an arteriometer
22:44and it's a beautiful piece.
22:46And what you do is you simply put it on the wrist
22:49where the artery is
22:51and you can measure the diameter of the artery on a gauge.
22:55Oliver was looking to cure low blood pressure
22:58using extracts from the adrenal glands,
23:01the glands that sit at the top of our kidneys.
23:06He had injected it into rabbits, all of whom had died as a result.
23:11But he was keen to test his extract on humans.
23:14And some people say he even used these on his son.
23:19Fortunately, his son survived and gave Oliver the results he needed.
23:25What he showed was that the effect of adrenal gland extracts,
23:29as measured on his arteriometer,
23:31caused a narrowing of the arteries
23:34and a resultant significant increase in the blood pressure.
23:38What we now know is that Oliver was measuring the effect of adrenaline.
23:43This chemical is released by a gland that sits on top of the kidneys.
23:47It produces a signal to get the heart beating faster
23:51and the blood flowing more quickly.
23:55Being able to measure the effects of adrenaline was an amazing breakthrough.
24:00But the mechanism by which it and other hormones worked was still a mystery.
24:06It would be solved just a few years later.
24:11But at a terrible price.
24:16Sadly, the crucial research to get us there
24:19would come out of one of the most scandalous practices
24:23in the history of medicine.
24:26This is the oldest operating theatre in England.
24:29And in places like this across Europe,
24:32women were undergoing oophorectomy.
24:35That's the removal of both ovaries for such conditions
24:40as hysteria, anorexia, anxiety and even nymphomania.
24:48And they thought that the ovaries
24:50were a source of all sorts of mental disabilities,
24:54physical disabilities and all sorts of things.
24:57So they simply took out the ovaries of women.
25:00And the reason they did this was because of a huge misconception
25:05all to do with the nervous system.
25:08The general view was that the nervous system
25:10governed all parts of the body, including the brain.
25:13The glands were part of this system.
25:16And the ovaries in particular were the nerve centres
25:19governing each and every woman.
25:22Amazingly, it's estimated that 150,000 women across Europe
25:27had this operation to try and cure them of their womanly ailments.
25:32But far from this, they developed fresh complications.
25:36And of course, if you take out the ovaries of women,
25:39it causes early menopausal symptoms.
25:42So in fact, women were back to square one on it.
25:46Doctors wanted to know why oophorectomies were causing this problem.
25:52While trying to find a solution, one man conducted experiments
25:56that would turn accepted science on its head.
26:00Joseph Halban undid the idea that glands communicated through nerves.
26:05And in doing so, he finally gave us the first clear picture
26:10of how the hormone system works.
26:14What Halban did was he took out the ovaries and the bits of the uterus,
26:18a little bit of the womb,
26:20and he transplanted these under the skin of young guinea pigs.
26:25And what he showed is that the ovaries and the uterus and the womb
26:32showed changes that you would expect to be if it was in situ,
26:38in the animal from which it came from.
26:41This proved that the ovaries worked if they were moved from their original site.
26:46More importantly, they carried on working
26:49even when there were no nerves connecting them to the rest of the body.
26:53Halban's discovery effectively put an end to oophorectomies.
26:58And it had a huge implication for the story of hormones as well.
27:03By this means, he showed that the ovaries weren't controlling things by nerves.
27:09Instead, by internal secretions,
27:13chemical messengers which move around the body in the blood,
27:17affecting distant parts.
27:20These secretions put together made a new system,
27:25the endocrine system.
27:28The definition of this new system was the final piece of the jigsaw for hormones.
27:34And with the turn of the 20th century,
27:37science had finally caught up with the forgotten observations Berthold had made.
27:43His work on cockerels,
27:46Horsley and Murray's experiments with thyroid glands,
27:49George Oliver's discovery of adrenaline,
27:52and now Halban.
27:55All of it came together to give us a modern understanding
27:59of a separate system of internal secretions constantly at work within our bodies.
28:07All that was now needed was to give these secretions a name.
28:13The story goes that at a university dinner in Cambridge,
28:17Ernest Starling, a leading physiologist of the day,
28:21coined the term that we've all come to use.
28:25As Starling sat talking with a colleague,
28:28they both struggled to find a name for these secretions
28:31that could pass to another part of the body and stimulate it directly.
28:36A scholar of ancient Greek just happened to pass by,
28:40and so they asked him.
28:42Someone said, well, they ought to call it something like homeo,
28:45which is the Greek word for I excite or stir up.
28:49And interestingly, Starling then gave a lecture at the Cronin Society
28:54and suddenly used the word hormone.
28:57No one had heard of it before, and that was it.
29:01The name stuck, and today we've all heard of hormones
29:06but we may not realise just how fundamental they are.
29:10Every form of life that has more than one cell, every plant,
29:14every animal, from an earthworm to a killer whale, uses hormones.
29:19There are more than 80 known hormones in humans alone,
29:23and they all have vastly different roles.
29:27If you're feeling stressed, that's one of the stress hormones, cortisol, at work.
29:32If you're preparing for exercise, adrenaline will kick in,
29:36that well-known fight-or-flight hormone.
29:39Hormones even have a hand in the bonding process,
29:43that one's oxytocin.
29:46But what are hormones?
29:49Well, there are different types, amines, peptides and steroids,
29:54and every single hormone has a different molecular structure.
30:00What unites them is how they work.
30:04Each hormone is aimed at a particular target cell.
30:08Strange as it may be, let's imagine I'm a hormone heading for my target.
30:13Each hormone flows through the bloodstream, passing over billions of cells.
30:18But they will only have their desired effect when they reach the right one,
30:22a cell that matches their specific chemical structure.
30:26You see, hormones only work at specific cells.
30:31Anywhere else, it's like trying to unlock a door with the wrong key.
30:36OK, wrong cell. Let's try that again.
30:43At these specific target cells, the key fits perfectly,
30:48and the hormone effectively unlocks the cell to get it working.
30:53Once the hormone acts on its target cell,
30:57it can change the way it behaves to make it perform a specific task.
31:02For example, when adrenaline reaches the heart, it makes it beat faster.
31:08Each hormone has its own unique role.
31:13Hormones have many different actions and many different timescales of action.
31:20So adrenaline has an effect on the heart for only a few minutes,
31:24whereas estrogen, secreted every day, has effects which last for years.
31:32Building up over long timescales like this,
31:35some hormones can have dramatic effects on our body,
31:39as one of my former patients can help to demonstrate.
31:43At 7'6", this is Chris Greener, one of Britain's tallest men.
31:50And here he is with our film's director, James, who's a good 5'9".
31:57Chris leads a healthy, if unusual, life.
32:00When people say to me, what's the problem with being tall?
32:03I say, I'm getting close, I have to have everything made to measure.
32:07I've had this problem for a long time.
32:11I've had this problem for, well, the best part of 50 years.
32:16When I left primary school, I was taller than most of the teachers.
32:20I just thought that I would stop growing, but I didn't.
32:26Chris's condition, called acromegalic gigantism,
32:30we now know is caused by overproduction of growth hormone,
32:34which meant that he kept growing and growing and growing well into his 20s.
32:39When I started work, I was 6'7".
32:41And when I was named tallest man, I was about 7'5".
32:44So I grew about 10 inches in seven years.
32:47Some of those years, I was probably growing in excess of two inches a year.
32:51It was by studying people like Chris
32:54that the mysterious role hormones play in growth was unraveled.
33:02The story starts in the 1780s with a man similar in stature to Chris.
33:09When Irishman Charles Byrne came to London to earn a living as a human curiosity,
33:16he quickly attracted the attention of a notorious scientist and collector called John Hunter.
33:24Going against Byrne's dying wish to be buried at sea,
33:28Hunter stole his body and displayed the skeleton in a museum.
33:35And, as unethical as this was, it did leave scientists an invaluable clue.
33:43More than a century later, in 1909,
33:46the brilliant neurosurgeon Harvey Cushing tried to explain why Byrne had grown so tall.
33:53He used the skull to suggest that the cause might lie within a tiny gland
33:58that's hidden at the base of the brain.
34:00It's called the pituitary,
34:02and it's incredibly difficult to find, as pathologist Dr Susie Lishman explains.
34:08This is a human brain,
34:10and you can see that there's an amazingly complex and rich network of nerves
34:14controlling all of our movement, our sensations, and our higher function.
34:19So, where does the pituitary gland fit into all this?
34:22Well, it's not quite as easy to see,
34:25and the only clue we've really got is this very short stalk.
34:30This is a pituitary stalk, and this is where the pituitary gland is attached.
34:34We had to remove it when we removed the brain.
34:37Now, if we have a look at the pituitary,
34:41here it is, a tiny organ around the size of a baked bean
34:45that sits on that stalk at the base of the brain,
34:48and I think you can just see the stalk that attaches it to the brain.
34:53Back in the 1900s, Cushing didn't really fully understand what the pituitary did,
34:59but he was convinced it was important because of where it was.
35:04And if we look in the base of the skull,
35:07we can see where the pituitary nestles in this area called the pituitary fossa.
35:12So, it's very carefully protected by a ring of bone
35:15to make sure that it doesn't get damaged.
35:17The protective bone layer convinced Cushing of the pituitary's importance,
35:22and that here lay the explanation for Charles Byrne's unusual height.
35:27And that's what was so interesting when Harvey Cushing examined the skull of Charles Byrne.
35:32Instead of having this small bean-sized area, there was a much, much bigger hole,
35:37and that's because the bone had been eroded,
35:40and Cushing deduced that that was because he'd had a pituitary adenoma or tumour
35:44that had grown, forcing the bone away.
35:47Cushing deduced, correctly as it turns out,
35:50that Byrne's height was due to this tumour on the pituitary,
35:55causing it to overproduce a hormone that tells our bodies to grow.
36:00A similar tumour had caused Chris Greener's height.
36:06As with the Irish giant, the tumour caused the pituitary to carry on pumping
36:11excessive quantities of growth hormone long past his teenage years.
36:16They put it on the machine, pressed the button, and the needle went,
36:20bing, off the end.
36:22They reckon I had over 200 growth hormones per unit of blood,
36:27when the average has been about 15, plus or minus a couple.
36:30Charles Byrne died at the age of 22, with his tumour still untreated.
36:35But in Chris's case, we were able to destroy his tumour with radiotherapy,
36:40and he stopped growing, and he's still going strong at the age of 70.
36:46Conditions like Chris's are fascinating.
36:50Though incredibly rare, they serve to emphasise
36:53just how important hormones are.
36:56And, as we shall see, the next breakthrough in our understanding of hormones
37:01quite literally transformed the lives of millions.
37:06This is a vial of human insulin.
37:09It's a hormone, probably the best-known hormone of them all.
37:13Without it, you develop diabetes.
37:16If that's treatable now, before the discovery of insulin,
37:19diabetes was a death sentence.
37:24For children who don't make the hormone insulin,
37:27sugar that would otherwise be absorbed as energy
37:31passed straight through their body into their urine.
37:36This is why the disease is called diabetes.
37:39The most common form, diabetes mellitus,
37:42literally means a sweet fountain,
37:46and the urine of a sufferer tastes sweet.
37:50Without the ability to store this vital energy,
37:53the child slowly wasted away to nothing,
37:56and never survived beyond their teens.
38:00It was incredibly difficult to find a cure to diabetes,
38:04even though there was evidence that one organ in particular,
38:07the pancreas, might be at the root of it.
38:11In the late 19th century,
38:13German physiologists and clinicians removed the pancreas from dogs
38:18and showed that they got diabetes.
38:21Now this led the way to identifying the pancreas
38:25as the source of raising blood sugar levels,
38:29i.e. becoming diabetic.
38:33This is a pig's pancreas,
38:35and it's about the same size and shape as a human pancreas,
38:38which is located in the upper part of the tummy at the back.
38:43And it's an amazing organ because it has two main functions.
38:47One is to produce digestive juices
38:50which enter the stomach through the pancreatic duct there,
38:54and the other is to produce insulin which controls sugar levels.
39:00This presented a problem for anybody who wanted to use the pancreas
39:04as a potential cure for diabetes.
39:07But the trouble with the pancreas is that
39:10most of the pancreas is made up of cells
39:13that secrete digestive enzymes.
39:15So if you'd have just mashed up the pancreas,
39:19there would have been virtually no insulin in it.
39:22All it would have been would have been, in fact, digestive juices.
39:27So who was the genius to crack this problem
39:30and earn what was the first Nobel Prize in endocrinology?
39:34Frederick Banting was in fact the unlikeliest of medical pioneers.
39:39He certainly didn't hit on his revolutionary cure for diabetes
39:43while working in a well-funded lab.
39:46Rather, he was a failing GP in Ontario in Canada.
39:53He was heavily in debt and would subsidize his income
39:56by giving lectures to medical students.
39:59And yet he was responsible for one of the most sensitive
40:03and dramatic discoveries in the whole of endocrinology.
40:08During his research for one of these lectures,
40:11he just happened to come across an article
40:14in the little-known publication Surgery Gynaecology and Obstetrics.
40:18This referred to the possibility of stopping
40:21the digestive function of the pancreas,
40:24effectively killing off the enzymes
40:27and just leaving the hormone-producing cells to do their work.
40:31He spent the day slogging over his notes,
40:34thinking how the body controls sugar
40:37and, in particular, how the pancreas deals with it.
40:43He went to bed with these thoughts still running through his mind
40:47and woke quite suddenly with a surprising revelation.
40:56And this was Frederick Banting's Eureka moment.
41:00These are the words of a note he wrote in the middle of the night.
41:04He said, Diabetes felt wrong.
41:07He was an appalling speller, apparently, but it was the middle of the night.
41:11Ligate the pancreatic ducts of dogs.
41:14Keep dogs alive till the acinides degenerate,
41:17leaving the islets.
41:20Try to isolate the internal secretion of these
41:23to relieve glycosuria.
41:26You need to be a doctor to understand that.
41:29These were the first steps in the cure to diabetes.
41:33He suddenly thought, if I tie off the duct
41:36that produces all these digestive enzymes from the pancreas,
41:40perhaps they might degenerate
41:44and I could, therefore, isolate
41:47the few cells or islets that produce insulin
41:51and thereby produce an insulin supplement.
41:56What Banting did was to operate on dogs
41:59and surgically tie off the pancreatic duct there.
42:03He kept them alive for six weeks
42:06and at the end of that time, the digestive enzyme cells had died
42:10and he was essentially left with a pancreas
42:13that was just producing insulin.
42:16Amazingly, when trialled on animals,
42:19extract from this dog pancreas
42:22proved Banting's theory was right
42:25and by January 1922, he was ready to see
42:28whether the same extract would work on humans.
42:33Leonard Thompson had been a diabetic from a very early age
42:37and in 1921, when he was 14,
42:40he was admitted to Toronto General Hospital,
42:43days away from death.
42:46He looked so thin, some people thought he was a famine victim.
42:49He was pale, his hair was falling out
42:52and he had a characteristic of diabetes
42:55and it was at that stage that he and his father
42:58agreed to have Banting's new experimental treatment
43:01containing insulin of what was described
43:04as thick brown muck.
43:07After a little refinement,
43:10this so-called muck, still made from dogs' pancreas,
43:14gave Thompson a whole new lease of life.
43:19And here's a picture of Leonard Thompson.
43:22This is after he started treatment with insulin
43:25and he should have been dead.
43:28But happily, he was the first patient to be successfully treated
43:31and it's wonderful because I've never seen a picture
43:34of Leonard Thompson before.
43:37Now produced synthetically,
43:40insulin has gone on to save the lives of millions.
43:43By any measure, a complete medical triumph.
43:46In the 1920s, however, it opened the floodgates
43:49to a new wave of hormone research
43:52with others hoping to find more miracle cures.
43:57Sadly, as we've seen before,
44:00this quest can have very unwelcome consequences.
44:04After this great success,
44:07we go from the sublime to the core blimey
44:10because endocrine science, for a bit,
44:14is seriously off track.
44:17The days of Brown sick hard may have been long behind us,
44:20but the hope for a secret to eternal youth remained.
44:24And with the miraculous survival of Leonard Thompson
44:27and other diabetics like him,
44:30the idea grew that if replacing missing hormones
44:33could cure the sick,
44:36surely increasing normal levels could enhance the healthy.
44:39Kew,
44:42one of the most bizarre fads in medical history.
44:46All across Europe and indeed the world,
44:49men began to subject themselves to an operation
44:52which was extremely perverse.
44:55What they wanted to do was to recapture their youth.
45:01This is the Prater in Vienna,
45:04the oldest amusement park in the world.
45:08Surprisingly, in the early 20th century,
45:11it was the site of a laboratory
45:14which carried out quite remarkable experiments.
45:20The Biological Research Institute on the grounds of this park
45:23also went by the nickname of the Vivarium.
45:28And it was here that physiologist Eugene Steinack
45:31developed a procedure
45:34which he claimed could reverse the ageing process.
45:38This lab was particularly interested
45:41in changing the body's natural processes.
45:49Steinack proposed a very similar technique
45:52to the one Banting had used
45:55to obtain insulin in the pancreas,
45:58tying off the duct from a gland
46:01to isolate one particular hormone within.
46:04This time, however, he wanted to isolate
46:07testosterone, and for that,
46:10he had a very different organ in mind.
46:13Steinack's procedure was to tie off the tube
46:16carrying the sperm, in modern parlance a vasectomy.
46:19What he thought would happen was that this would create
46:22more room for the hormone-producing cells in the testis,
46:25and this would give his patients more vigour.
46:30Hard as it is to believe, the Steinack was a sensation.
46:34With people flocking to have it done on themselves,
46:37including some rather high-profile patients.
46:41Among them was the famous poet
46:44William Butler Yeats.
46:48At 69, Yeats was in poor health
46:51and really quite depressed,
46:54and he had writer's block.
46:57But after the procedure,
47:00he noticed a huge increase in his creative powers
47:03as well as his sexual desire.
47:06Interestingly, some people think Yeats wrote
47:09his best poetry after the procedure.
47:14A young man in the dark am I,
47:17but a wild old man in the light.
47:20Then said she to that wild old man
47:23his stout stick under his hand.
47:26Love to give or to withhold
47:29is not at my command.
47:33And it wasn't just his birch tree.
47:36A few months after the Steinack,
47:39Yeats took up with an actress who, at 27,
47:42was 42 years younger than him.
47:45Had Steinack stumbled on the secret of eternal youth?
47:53Well, of course he hadn't.
47:56And just as with Bran Secard,
47:59there was no way to reproduce the results he'd claimed.
48:03We now know that there's no scientific rationale
48:06and that it was another scientific blind alley.
48:10Endocrinology had come a long way
48:13by the time we reached Steinack.
48:16But his procedure failed
48:19because his understanding of how hormones work
48:22was far too simplistic.
48:25Steinack thought that the more testosterone
48:28there was circulating around the body,
48:31the more testosterone there was circulating.
48:34But the problem was, it wasn't that simple.
48:37First, Steinack was wrong to think
48:40that tying off the sperm ducts
48:43caused an increase in the male sex hormone testosterone.
48:46But more crucially, even if he could have raised its levels,
48:49he completely misjudged what would happen.
48:52There's only one part of the endocrine system
48:55he hadn't understood,
48:59Steinack had no idea
49:02how hormones are regulated.
49:05But the publicity around his claims
49:08spurred on a huge amount of research
49:11and out of this came an explanation
49:14of where he'd gone wrong.
49:17And more than this, it gave a new understanding
49:20of a key role of a tiny gland we've met before,
49:23the pituitary.
49:26As well as producing growth hormone,
49:29the pituitary has the crucial job
49:32of ensuring that the levels of many hormones
49:35never get too high or too low.
49:38And that's why Steinack's technique
49:41couldn't possibly have worked.
49:44Even if you overload the endocrine system with testosterone,
49:47normally the pituitary will step in
49:50to bring the levels back down again to normal.
49:54In many ways,
49:57the pituitary works just like a household thermostat.
50:00It can sense if hormone levels have gone wrong
50:03and send messages to some of the major glands,
50:06getting them to produce more or less hormone as needed.
50:11The discovery of this aspect of the pituitary
50:14was a real milestone in my field.
50:17Even when I was a medical student in the 60s,
50:20this tiny gland was still considered
50:23the linchpin to hormone regulation.
50:26But what I love about this story
50:29is that it never stands still.
50:32And even in the last few years,
50:35research has uncovered an entirely new system of regulation
50:38which has led us to broaden our views.
50:42In fact, this system is challenging our perceptions
50:45of not only how we control hormones,
50:48but indeed how hormones control us.
50:52Professor Sadaf Farooqui
50:55has been working at the cutting edge of hormone research
50:58for more than a decade.
51:01She and her team have been studying
51:04the role of hormones in obesity.
51:07And in this condition,
51:10hormones work in a much more surprising way
51:13than we ever imagined.
51:16So the first real breakthrough emerged
51:19with the discovery of a completely new hormone called leptin
51:22which was first found in mice which were severely obese.
51:25And this really paved the way
51:28for finding out an entirely new system
51:31for how weight is regulated.
51:34And this system depends upon the hormone leptin
51:37which is actually made by our fat.
51:40It was a discovery that was entirely unprecedented.
51:43A hormone produced not by a gland,
51:47and no one thought had any part in the endocrine system.
51:52And this is not something we had realised before.
51:55We didn't know that fat could make hormones.
51:58We knew that fat is there to store extra calories.
52:01But this was a really important discovery
52:04because we learnt that fat could make a hormone
52:07that circulated in the bloodstream
52:10and acted in the brain to control our weight.
52:13Incredibly, with this hormone,
52:16fat cells can actually eat
52:19by setting up their own feedback loop with the brain.
52:22It works like this.
52:25Leptin is constantly being produced by our fat cells.
52:28And the more fat stores we have in general,
52:31the more leptin flows in the blood.
52:34This essentially tells our brain
52:37that we've eaten enough and we lose our appetite.
52:40But where Sadaf's work comes in
52:43is a bit of a mystery,
52:46and for some reason the fat cells don't make leptin.
52:49Sadaf is still working to understand
52:52all the reasons behind how this can happen.
52:55But by figuring out one cause in particular,
52:58she has already made a fantastic discovery.
53:01Remarkably, a patient's inability to produce leptin
53:04can, in some cases, come down to their genes.
53:08A key part of how we discovered
53:11the role of the hormone leptin was using genetics.
53:14And we were able to look at the DNA of patients
53:17and find that they had a mutation or a gene defect
53:20that was disrupting the hormone leptin.
53:23And this was the cause of their weight problem.
53:26In the rare case that someone has this faulty gene,
53:29they will be unable to control their appetite.
53:32And so will eat more than their body needs.
53:35And so will eat more than their body needs.
53:38And this will inevitably mean that they become obese.
53:41Up until that time, most people thought
53:44that actually your tendency to gain weight
53:47was purely down to self-control.
53:50It was purely down to the food you eat
53:53and the exercise you do,
53:56and there wasn't really any biology involved.
53:59Actually, what we showed through the discovery of leptin
54:03is that hormones are affecting our weight
54:06and they do so by affecting our appetite.
54:09And leptin is a key regulator of appetite.
54:12It's an incredible discovery
54:15that hormones are a key factor
54:18in our ability to maintain a healthy weight.
54:21And the fact that even a person's appetite
54:24can be marshaled by a hormone
54:27has given people new hope in the battle against obesity.
54:30That really meant that we could find treatments for those patients
54:33and we were able to give them leptin back.
54:36And we did that by giving them injections,
54:39which they take twice a day,
54:42and thankfully it's worked incredibly well.
54:45And now they live entirely normal lives,
54:48they are a normal weight,
54:51and many of the other health problems
54:54that they suffered with have been corrected.
54:57Many of these guys have no control over their weight.
55:00It's a striking example of the power of hormones.
55:03And alongside other recent breakthroughs,
55:06it suggests that we are on the verge of discovering
55:09a whole range of new hormones
55:12with potentially breathtaking capabilities.
55:18Well, it's fascinating, really,
55:21because we've come from understanding
55:24what hormones were, i.e. from Brown-Seckard
55:27and everyone mashing up a few glands,
55:30to realising that actually most of our body now produces hormones.
55:35And I think in the future
55:38the discovery of new hormones is going to be absolutely vast.
55:45Work like Sadaf's forces us to reassess
55:48whether what we do is down to free will
55:51or simply our hormones.
55:54And it's a heady thought to think that one day
55:57we might harness the power of these chemicals
56:00to control almost every aspect of our biology.
56:05But there are lessons to be learnt from the history of hormones.
56:08Stories like oophorectomies
56:11and the search for eternal youth
56:14remind us that a little bit of knowledge
56:17is a decidedly dangerous thing.
56:20Let's assume that we have all the answers.
56:23As soon as we think we understand hormones completely
56:26a new discovery will come along
56:29and prove just how little we know.
56:32It's extraordinary that the study of hormones
56:35is only just over 100 years old.
56:38There have been some amazing discoveries
56:41and yet it's a science that is in its infancy.
56:45And for me the ongoing fascination
56:48is that it's going to be many years
56:51before hormones reveal all their secrets.
57:14Transcription by ESO. Translation by —