0:00:10 > 0:00:14There is a mysterious set of chemicals that flow through
0:00:14 > 0:00:16every part of our bodies.
0:00:19 > 0:00:24They can rule our lives and shape our destinies.
0:00:24 > 0:00:31They turn children into adults, they govern our appetites
0:00:31 > 0:00:35and they even affect our passions.
0:00:35 > 0:00:41They are called hormones and they are fundamental to making us
0:00:41 > 0:00:43who we are.
0:00:45 > 0:00:47I'm John Wass,
0:00:47 > 0:00:52a professor of endocrinology - that's the study of hormones.
0:00:52 > 0:00:56Hormones have been my professional life for 40 years,
0:00:56 > 0:00:59and they're absolutely fascinating.
0:00:59 > 0:01:03To a greater or lesser extent, they control everything in your body.
0:01:05 > 0:01:08How we unravelled the ways hormones work is one of the most
0:01:08 > 0:01:12fascinating stories in the whole history of medicine.
0:01:12 > 0:01:13COCK CROWS
0:01:16 > 0:01:20It's a story that involves bizarre experiments,
0:01:20 > 0:01:23and quite remarkable characters.
0:01:23 > 0:01:27Along the way there have been some horrific wrong turns.
0:01:29 > 0:01:35And some of the worst examples of opportunism and quackery.
0:01:35 > 0:01:38Spermin Liquidim...
0:01:38 > 0:01:40The hormones of two testicles.
0:01:40 > 0:01:43HE GIGGLES
0:01:43 > 0:01:46But there have been some inspired moments of genius,
0:01:46 > 0:01:50and heart-warming tales of survival.
0:01:50 > 0:01:53And here is a picture of Leonard Thompson,
0:01:53 > 0:01:56and he should have been dead.
0:01:56 > 0:02:02Today, hormones are at the cutting edge of medical science
0:02:02 > 0:02:06and almost daily, we are learning that their effects are
0:02:06 > 0:02:09more widespread than we ever imagined.
0:02:11 > 0:02:14For me, this is a personal journey, as well,
0:02:14 > 0:02:17it's a story I've wanted to tell all my life.
0:02:17 > 0:02:23To share and instil my enthusiasm for this subject, which affects
0:02:23 > 0:02:28each and every one of us, is the most wonderful opportunity.
0:02:28 > 0:02:33Hormones are a crucial part of our biology and to understand them
0:02:33 > 0:02:36is to better understand ourselves.
0:02:50 > 0:02:52We've all heard of hormones,
0:02:52 > 0:02:55but most of us don't think about them every day.
0:02:55 > 0:02:59And for something so fundamental to our lives,
0:02:59 > 0:03:03our understanding of hormones is remarkably recent.
0:03:03 > 0:03:07The hormone system isn't an anatomical thing like the skeleton,
0:03:07 > 0:03:10like the nervous system, like the cardiovascular system.
0:03:10 > 0:03:14It's something which you don't see, so anatomically it's different.
0:03:14 > 0:03:18I mean, it's easy being a cardiologist. They have
0:03:18 > 0:03:20pain in the chest, there's something wrong with their heart
0:03:20 > 0:03:23But with endocrine conditions it's completely different.
0:03:23 > 0:03:25I think that's one of the reasons why
0:03:25 > 0:03:28it's one of the last of the systems, if you like, to be discovered.
0:03:30 > 0:03:34This endocrine or hormone system, though invisible, is
0:03:34 > 0:03:39one of the most important factors in running and regulating our bodies.
0:03:42 > 0:03:46The way we uncovered its secrets is a great medical detective story.
0:03:46 > 0:03:50It's full of unexpected twists.
0:03:52 > 0:03:55And I'm going to pick up the trail in the 1730s,
0:03:55 > 0:04:00not with a great doctor and a brilliant experiment, as you might expect,
0:04:00 > 0:04:04but in one of my favourite cities on the planet,
0:04:04 > 0:04:08with a really surprising story.
0:04:12 > 0:04:15In all my years as a doctor, and an opera lover,
0:04:15 > 0:04:17I never dreamed I'd be standing on the stage
0:04:17 > 0:04:22of the Theatre an der Wien, one of the world's great opera houses.
0:04:24 > 0:04:27I want to play you and extraordinary sound.
0:04:27 > 0:04:29PIANO MUSIC AND SOPRANO VOICE
0:04:29 > 0:04:34Believe it or not this is the voice of a grown man, over six-feet tall.
0:04:34 > 0:04:40Made in 1902, this is the only recording of a singer of this kind.
0:04:44 > 0:04:50But arguably its greatest proponent lived in the 1730s.
0:04:50 > 0:04:55He was a true musical star and his name was Farinelli.
0:05:05 > 0:05:10This is the sound that Farinelli would have made.
0:05:10 > 0:05:16Almost supernatural. Amazingly pure, gentle, sublime,
0:05:16 > 0:05:20and yet forceful, because he was a fully grown man.
0:05:23 > 0:05:26The reason for this extraordinary voice is that he was
0:05:26 > 0:05:31a castrato - Farinelli was castrated before puberty,
0:05:31 > 0:05:37in order to maintain the purity of that voice, which didn't break.
0:05:43 > 0:05:46When a boy reaches puberty,
0:05:46 > 0:05:49his voice can drop by as much as a whole octave...
0:05:49 > 0:05:50# Ave Maria... #
0:05:55 > 0:05:59..Making him unable to hit the high notes of the soprano range.
0:06:02 > 0:06:08But, since Farinelli was castrated before this change could happen,
0:06:10 > 0:06:16his voice remained high, even as he grew to full adulthood.
0:06:17 > 0:06:20Amazingly, this shocking procedure continued
0:06:20 > 0:06:23until the early 20th century.
0:06:25 > 0:06:29And for many boys, castrated in the hope they would be the next
0:06:29 > 0:06:34Farinelli, the effects were both dramatic and permanent.
0:06:34 > 0:06:39It wasn't just his voice, there were other really important changes,
0:06:39 > 0:06:43which you can see in this wonderful painting. You can see that
0:06:43 > 0:06:48he had a straight hairline, like a woman, and didn't have the "V" shape
0:06:48 > 0:06:53of a man. He's covered his lack of an Adam's apple with a silk scarf.
0:06:53 > 0:06:58And castration even affected how much Farinelli grew.
0:06:58 > 0:07:03He had an enormous chest, also his really long arms,
0:07:03 > 0:07:07and the legs, too, will have been very long - they carry on growing.
0:07:07 > 0:07:11And all of this because of castration.
0:07:12 > 0:07:16Castrati serve as a very dramatic demonstration of what happens
0:07:16 > 0:07:20when you remove the testicles, or testes, from humans.
0:07:22 > 0:07:24And, of course,
0:07:24 > 0:07:28people had observed the effects of castration on cattle for centuries.
0:07:30 > 0:07:34But, amazingly, there was no scientific explanation
0:07:34 > 0:07:39for why this happened, right into the 19th century.
0:07:39 > 0:07:43So this is the big question that completely baffled people.
0:07:43 > 0:07:47How on earth could the testes affect so many parts of the body
0:07:47 > 0:07:51from your vocal cords to the length of your limbs?
0:07:57 > 0:07:59Talk about a fall from grace -
0:07:59 > 0:08:04I've gone from grand opera to chasing chickens.
0:08:07 > 0:08:10But there is a good reason.
0:08:14 > 0:08:20In 1849, a German physiologist called Arnold Berthold did
0:08:20 > 0:08:24some extraordinary experiments on chickens which would reveal
0:08:24 > 0:08:28the mechanism by which castration could affect the whole body.
0:08:37 > 0:08:40Berthold was the Professor of Medicine in Goettingen,
0:08:40 > 0:08:43that well-known university town in the middle of Germany,
0:08:43 > 0:08:46and he also ran the Department of Zoology,
0:08:46 > 0:08:49where he came across some birds called capons.
0:08:51 > 0:08:53The capons' meat was incredibly tender,
0:08:53 > 0:08:57a real delicacy in early 19th century Europe, and the reason
0:08:57 > 0:09:02for this is, like a castrato, they'd had their testes removed.
0:09:04 > 0:09:07Castration had a wide variety of effects on these birds.
0:09:08 > 0:09:13Compared to regular cockerels, they became docile, meek even,
0:09:14 > 0:09:17and lost all their sexual appetite.
0:09:19 > 0:09:22But the main reason Berthold chose capons for his experiments was
0:09:22 > 0:09:26because they had an obvious physical marker, which made them
0:09:26 > 0:09:30easy to tell apart from cockerels, even at a glance.
0:09:33 > 0:09:35This is Bernard,
0:09:35 > 0:09:40a real bloke of a bird, I can tell you, he's itching to chase hens.
0:09:40 > 0:09:43You can see his aptly named comb on the top of his head,
0:09:43 > 0:09:46his wattle under his beak.
0:09:46 > 0:09:48He's a full-blown male.
0:09:48 > 0:09:53Capons were completely different - they had droopy combs
0:09:53 > 0:09:55and droopy wattles.
0:09:55 > 0:09:57BERNARD CROWS
0:09:57 > 0:10:00Armed with this simple measure of masculinity,
0:10:00 > 0:10:03Berthold began a series of experiments to see
0:10:03 > 0:10:06if he could halt or even reverse the effects of castration.
0:10:06 > 0:10:09What he wanted to do is to try
0:10:09 > 0:10:11and reverse the changes that had gone on.
0:10:11 > 0:10:14So he took the testes out of young cockerels,
0:10:14 > 0:10:20then what he did was to transplant testes into cockerels,
0:10:20 > 0:10:25not within their normal place in the body but in the abdomen,
0:10:25 > 0:10:30and surprisingly, he found it would maintain their sexual activity,
0:10:30 > 0:10:36their aggressive behaviour, and also maintain their wattles and combs.
0:10:36 > 0:10:38With these birds,
0:10:38 > 0:10:42Berthold now had a way to answer the completely crucial question,
0:10:42 > 0:10:48how were the testicles able to affect distant parts of the body?
0:10:49 > 0:10:55When Berthold came to do the autopsy on these birds, he found,
0:10:55 > 0:10:59quite surprisingly, that the testes he'd put back into the abdomen
0:10:59 > 0:11:01had redeveloped their own blood supply -
0:11:01 > 0:11:04the blood vessels had grown round the testes.
0:11:04 > 0:11:08So the key deduction was, that whatever effects were happening,
0:11:08 > 0:11:11were happening through the blood.
0:11:14 > 0:11:18And what Berthold showed, interestingly,
0:11:18 > 0:11:21was there were obviously some chemicals
0:11:21 > 0:11:26released from the testes that reacted at other parts of the body.
0:11:26 > 0:11:31We now know that Berthold was seeing the action of the male sex hormone,
0:11:31 > 0:11:36testosterone, which, released into the blood in huge amounts
0:11:36 > 0:11:40at puberty, effectively turns boys into men.
0:11:40 > 0:11:45No-one had any concept that chemicals alone could have
0:11:45 > 0:11:48such a dramatic effect on the whole body.
0:11:50 > 0:11:53But, strangely, his findings didn't have much impact
0:11:53 > 0:11:55on the broader scientific community.
0:11:55 > 0:12:00And Berthold himself didn't conduct any further research
0:12:00 > 0:12:01into what he'd seen.
0:12:03 > 0:12:06These were fabulously interesting observations,
0:12:06 > 0:12:10and it's interesting that Berthold really didn't seem
0:12:10 > 0:12:13to think very much as to why they had occurred.
0:12:13 > 0:12:16So it was a huge, missed scientific opportunity
0:12:16 > 0:12:21and it was going to be many decades before there was an explanation.
0:12:21 > 0:12:26In the 20th century, scientists would rightly acknowledge
0:12:26 > 0:12:30Berthold as the first to describe how the testicles work.
0:12:30 > 0:12:34But, sadly, his contemporaries ignored his findings.
0:12:34 > 0:12:38Instead, they made bizarre claims about the testicles.
0:12:38 > 0:12:41And in particular, for men, at least,
0:12:41 > 0:12:45they thought they might be the source of eternal youth.
0:12:46 > 0:12:49Brown-Sequard's method...
0:12:49 > 0:12:51HE LAUGHS
0:12:51 > 0:12:55This extraordinary advertisement dates from the early 20th century
0:12:55 > 0:12:58claims to have found the power to rejuvenate old men.
0:13:00 > 0:13:02"Hormones of two testicles..."
0:13:02 > 0:13:03HE LAUGHS
0:13:03 > 0:13:05It's amazing. This is so funny.
0:13:10 > 0:13:12The story of this ridiculous claim,
0:13:12 > 0:13:15and its surprising consequences, begins in 1889
0:13:15 > 0:13:19in one of the most august institutions in Europe...
0:13:22 > 0:13:24..the Academy of Sciences in Paris.
0:13:25 > 0:13:29At a very formal occasion, a serious audience came to hear
0:13:29 > 0:13:34the announcement of one Charles Edouard Brown-Sequard.
0:13:39 > 0:13:42At the age of 72, and at the end of a long
0:13:42 > 0:13:46and distinguished career, as a scientist and a doctor,
0:13:46 > 0:13:49he will have been familiar with the wonderful surroundings
0:13:49 > 0:13:54in the Grand Salle de Sciences, the Academy of Sciences in Paris,
0:13:54 > 0:13:57as a large number of eminent professors
0:13:57 > 0:13:59gathered to hear him speak.
0:13:59 > 0:14:05What Brown-Sequard announced was a truly unbelievable experiment.
0:14:05 > 0:14:11He said he had prepared a concoction of the following three ingredients.
0:14:11 > 0:14:15'Blood of the testicular veins, semen
0:14:15 > 0:14:20'and juice extracted from a testicle, crushed immediately after
0:14:20 > 0:14:23'it has been taken from a dog or a guinea-pig.'
0:14:24 > 0:14:27The resulting blood and semen mixture,
0:14:27 > 0:14:30he injected into himself.
0:14:34 > 0:14:38This is what he told his astonished audience - that he
0:14:38 > 0:14:43had more strength and stamina, his concentration powers had improved
0:14:43 > 0:14:47and, as well, his mental energy was considerably better.
0:14:47 > 0:14:51Apparently there was shocked silence in the audience.
0:14:51 > 0:14:55But with an average age of 71, you can just imagine them thinking,
0:14:55 > 0:14:58"Oh, my goodness, that would be good."
0:14:58 > 0:14:59This had the potential to be
0:14:59 > 0:15:04the elixir of life, and a possible breakthrough of the century.
0:15:06 > 0:15:10The announcement sent the media into a complete frenzy
0:15:10 > 0:15:13and with public demand for this kind of cure-all remedy
0:15:13 > 0:15:18soaring across the globe, the papers were filled with articles
0:15:18 > 0:15:21and advertisements about it alike.
0:15:21 > 0:15:24Brown-Sequard was headline news throughout the whole world.
0:15:24 > 0:15:28The press asked, was this a genuine elixir of life?
0:15:30 > 0:15:32Of course, it wasn't!
0:15:32 > 0:15:36But it was a call to arms, signalling the start
0:15:36 > 0:15:40of a period of intense interest in the testicles and other related
0:15:40 > 0:15:42organs, whose extracts people thought
0:15:42 > 0:15:45could be used for medical purposes.
0:15:45 > 0:15:49By tapping into a public thirst for miracle cures,
0:15:49 > 0:15:52Brown-Sequard created a real phenomenon.
0:15:53 > 0:15:55This was called "organotherapy,"
0:15:55 > 0:15:59and involved the injection of various glands into people,
0:15:59 > 0:16:06often with very little scientific evidence, to cure various illnesses.
0:16:06 > 0:16:09But in the case of Brown-Sequard, no-one was able to repeat
0:16:09 > 0:16:13his results experimentally, and the dramatic effects he had claimed on
0:16:13 > 0:16:18his own body must have been down to nothing more than a placebo effect.
0:16:18 > 0:16:22Unfortunately, it's unlikely that the watery extracts would
0:16:22 > 0:16:26have contained any active substance at all.
0:16:26 > 0:16:31So, Brown-Sequard's extract couldn't possibly have worked.
0:16:31 > 0:16:36But the great interest it inspired in the effects of gland extracts
0:16:36 > 0:16:39did have lasting consequences.
0:16:39 > 0:16:43Throughout the next decade, the 1890s, there was a whole
0:16:43 > 0:16:46series of genuine scientific breakthroughs,
0:16:46 > 0:16:52ones that are a vital and extremely gratifying part of my job today.
0:16:54 > 0:16:58So this was a woman I was treating who had an underactive thyroid
0:16:58 > 0:17:01and one of her children sent me a card.
0:17:01 > 0:17:04"Thank you for listening to my mum and giving her back."
0:17:04 > 0:17:07And then her mother wrote, "I cannot thank you enough for giving me
0:17:07 > 0:17:10"my daughter back, my grandchildren their mummy back
0:17:10 > 0:17:13"and my son-in-law, his wife."
0:17:13 > 0:17:16And all I had done was to give her thyroid hormone.
0:17:16 > 0:17:18Lovely though it is to be thanked like this,
0:17:18 > 0:17:21I really don't deserve it.
0:17:21 > 0:17:24The real thanks should go to a pair of pioneering British doctors
0:17:24 > 0:17:29from the 1890s. They were the first people to actually use
0:17:29 > 0:17:32hormones to cure what, up until then,
0:17:32 > 0:17:36was a debilitating and horrific illness.
0:17:36 > 0:17:41This was the story of the first scintillating discovery
0:17:41 > 0:17:45which resulted in a successful treatment in endocrinology
0:17:45 > 0:17:49and it relates to the thyroid gland in the neck.
0:17:51 > 0:17:55The treatment focused on disorders known as myxoedema and cretinism.
0:17:55 > 0:18:00They're in fact similar conditions, which can leave sufferers physically
0:18:00 > 0:18:02and mentally disabled.
0:18:03 > 0:18:07They were relatively common even 100 years ago,
0:18:07 > 0:18:12and cretinism even featured as a tick box on the Victorian census.
0:18:15 > 0:18:20Fortunately, it is a disease that is completely manageable today
0:18:20 > 0:18:24and that's because of the work started by this man.
0:18:25 > 0:18:29Victor Horsley was born here in sunny old London,
0:18:29 > 0:18:33into a family of artistic aristocrats.
0:18:33 > 0:18:36But he had a huge social conscience
0:18:36 > 0:18:40and was a forcible advocate of free health care for all.
0:18:46 > 0:18:52But, for me, his most important work was on the thyroid.
0:18:52 > 0:18:54I'm going to explain what he did
0:18:54 > 0:18:56with the help of some props.
0:18:59 > 0:19:01These are sheep's thyroids,
0:19:01 > 0:19:05although when Horsley began his experiments he used monkeys.
0:19:05 > 0:19:09And what Horsley did was to remove the thyroid from some monkeys
0:19:09 > 0:19:11and showed that they developed changes of myxoedema
0:19:11 > 0:19:16just like humans - their hair fell out and they became more lethargic.
0:19:16 > 0:19:20With this proof, Horsley conclusively demonstrated
0:19:20 > 0:19:24that myxoedema was caused by thyroid deficiency.
0:19:25 > 0:19:27But beyond this,
0:19:27 > 0:19:30he then went on to suggest the bold step of transplanting
0:19:30 > 0:19:33tissue from sheep's thyroid,
0:19:33 > 0:19:37just like these, into human patients.
0:19:39 > 0:19:42Others across Europe took up the call and the practice
0:19:42 > 0:19:47of transplanting sheep's thyroids into people had some success.
0:19:47 > 0:19:50But this still wasn't a cure.
0:19:50 > 0:19:56It was potentially dangerous surgery and the benefits were short-term.
0:19:56 > 0:20:00So this was the problem - you can't carry on giving this
0:20:00 > 0:20:04every seven days, and the effects only lasted for that time.
0:20:04 > 0:20:09So the question was, how do we make that into a treatment?
0:20:10 > 0:20:14It actually took the work of one of Horsley's students,
0:20:14 > 0:20:18George Murray, to solve this problem in a highly unusual way.
0:20:20 > 0:20:24Murray's solution was to cut the thyroid up into tiny, little bits,
0:20:24 > 0:20:28put them in carbolic acid, stopper them overnight,
0:20:28 > 0:20:35and then use a common-or-garden handkerchief.
0:20:35 > 0:20:38And he used this handkerchief to strain these bits
0:20:38 > 0:20:43and produce what he described as "pink thyroid juice".
0:20:47 > 0:20:50This, in some ways, was a revolution.
0:20:50 > 0:20:53It meant that there was a cheap, effective way of treating
0:20:53 > 0:20:57these conditions of myxoedema and what resulted from cretinism.
0:20:57 > 0:21:00And it was cheap,
0:21:00 > 0:21:03because he obtained those thyroid glands from the abattoir.
0:21:03 > 0:21:07The most famous patient, we only know her as Mrs S,
0:21:07 > 0:21:10was 46 when Murray started treating her,
0:21:10 > 0:21:13and she had obvious myxoedema with a swollen face and pale skin.
0:21:13 > 0:21:16And Murray started giving her injections
0:21:16 > 0:21:19of sheep's thyroid juice twice a week.
0:21:19 > 0:21:23And within three months, there was a miraculous improvement in her
0:21:23 > 0:21:26appearance - her skin was less pale and she'd actually improved
0:21:26 > 0:21:31her energy such that Murray wrote in his notes that she could
0:21:31 > 0:21:34do the housework much more easily.
0:21:34 > 0:21:35Poor thing.
0:21:35 > 0:21:39Mrs S lived to the ripe old age of 74,
0:21:39 > 0:21:42which was a pretty good innings in 1890.
0:21:42 > 0:21:46Thyroid hormones, in contrast to testosterone, last several
0:21:46 > 0:21:52days in the blood, which is why these injections worked.
0:21:52 > 0:21:56And this made them the first successful treatment in our story.
0:21:56 > 0:22:01But really, Horsley and Murray had no idea what hormones were
0:22:01 > 0:22:04Though successful, they were only observing
0:22:04 > 0:22:09the effects of glands, with no understanding how they worked.
0:22:11 > 0:22:15To get us closer to this, it would take the invention of a truly
0:22:15 > 0:22:17ingenious device,
0:22:17 > 0:22:21one which was actually able to show a hormone at work.
0:22:27 > 0:22:30You could be forgiven for thinking that this was a Swiss
0:22:30 > 0:22:34masterpiece watch from the turn of the century.
0:22:34 > 0:22:39In fact, it's an amazing device invented by a physician
0:22:39 > 0:22:42from Harrogate called George Oliver.
0:22:42 > 0:22:45What this machine is called is an arteriometer
0:22:45 > 0:22:47and it's a beautiful piece.
0:22:47 > 0:22:51And what you do is, you simply put it on the wrist,
0:22:51 > 0:22:52where the artery is
0:22:52 > 0:22:56and you can measure the diameter of the artery on a gauge.
0:22:57 > 0:23:01Oliver was looking to cure low blood pressure using extracts
0:23:01 > 0:23:05from the adrenal gland - the glands that sit at the top of our kidneys.
0:23:07 > 0:23:12'He had injected it into rabbits, all of whom had died as a result,
0:23:12 > 0:23:15'but he was keen to test his extract on humans.'
0:23:15 > 0:23:20And some people even say he used these on his son.
0:23:20 > 0:23:25'Fortunately, his son survived, and gave Oliver the results he needed.'
0:23:25 > 0:23:29What he showed was that the effects of adrenal extracts,
0:23:29 > 0:23:34as measured on his arteriometer, caused a narrowing of the arteries,
0:23:34 > 0:23:39and a resultant significant increase of the blood pressure.
0:23:39 > 0:23:43What we now know is that Oliver was measuring the effect of adrenaline.
0:23:43 > 0:23:48This chemical is released by a gland that sits on top of the kidneys.
0:23:48 > 0:23:51It produces a signal to get the heart beating faster
0:23:51 > 0:23:54and the blood flowing more quickly.
0:23:56 > 0:23:58Being able to measure the affects of adrenaline
0:23:58 > 0:24:00was an amazing breakthrough.
0:24:00 > 0:24:04But the mechanism by which it and other hormones worked
0:24:04 > 0:24:05was still a mystery.
0:24:05 > 0:24:09It would be solved just a few years later...
0:24:11 > 0:24:13..but at a terrible price.
0:24:17 > 0:24:21Sadly, the crucial research to get us there would come out of one
0:24:21 > 0:24:25of the most scandalous practices in the history of medicine.
0:24:27 > 0:24:30This is the oldest operating theatre in England,
0:24:30 > 0:24:34and in places like this, across Europe, women were undergoing
0:24:34 > 0:24:39oophorectomy - that's the removal of both ovaries for such
0:24:39 > 0:24:44"conditions" as hysteria, anorexia,
0:24:44 > 0:24:49anxiety and even nymphomania.
0:24:49 > 0:24:53And they thought that the ovaries were a source of all sorts
0:24:53 > 0:24:57of mental disabilities, physical disabilities, and all
0:24:57 > 0:25:01sorts of things, so they simply took out the ovaries of women.
0:25:01 > 0:25:03And the reason they did this was
0:25:03 > 0:25:08because of a huge misconception, all to do with the nervous system.
0:25:08 > 0:25:11The general view was that the nervous system governed
0:25:11 > 0:25:14all parts of the body, including the brain.
0:25:14 > 0:25:18The glands were part of this system, and the ovaries, in particular,
0:25:18 > 0:25:23were the nerve centres governing each and every woman.
0:25:23 > 0:25:28Amazingly, it's estimated that 150,000 women across Europe
0:25:28 > 0:25:33had this operation to try and cure them of their womanly ailments.
0:25:33 > 0:25:37But far from this, they developed fresh complications.
0:25:37 > 0:25:40And of course if you take out the ovaries of women, it causes early
0:25:40 > 0:25:46menopausal symptoms, so in fact women were back to square one on it.
0:25:46 > 0:25:50Doctors wanted to know why oophorectomies
0:25:50 > 0:25:53were causing this problem.
0:25:53 > 0:25:56While trying to find a solution, one man conducted experiments
0:25:56 > 0:25:59that would turn accepted science on its head.
0:26:01 > 0:26:05Josef Halban undid the idea that glands communicated through
0:26:05 > 0:26:09nerves, and in doing so, he finally gave us
0:26:09 > 0:26:14the first clear picture of how the hormone system works.
0:26:14 > 0:26:18What Halban did was he took out the ovaries and bits of uterus
0:26:18 > 0:26:20and a little bit of the womb,
0:26:20 > 0:26:25and he transplanted these under the skin of young guinea pigs.
0:26:25 > 0:26:30And what he showed is that the ovaries, and the uterus,
0:26:30 > 0:26:35and the womb, showed changes that you would expect to be in
0:26:35 > 0:26:41if it was in situ in the animal from which it came from.
0:26:41 > 0:26:47This proved that the ovaries worked if moved from their original site.
0:26:47 > 0:26:50More importantly, they carried on working,
0:26:50 > 0:26:52even when there were no nerves connecting them
0:26:52 > 0:26:54to the rest of the body.
0:26:54 > 0:26:59Halban's discovery effectively put an end to oophorectomies
0:26:59 > 0:27:03and it had a huge implication for story of hormones as well.
0:27:03 > 0:27:08By this means, he showed that the ovaries weren't controlling things
0:27:08 > 0:27:15by nerves, instead by internal secretions, chemical messengers,
0:27:15 > 0:27:20which move around the body in the blood, affecting distant parts.
0:27:21 > 0:27:24These secretions, put together,
0:27:24 > 0:27:29made a new system - the endocrine system.
0:27:29 > 0:27:31The definition of this new system was the final
0:27:31 > 0:27:35piece of the jigsaw for hormones.
0:27:35 > 0:27:38And with the turn of the 20th century, science had finally
0:27:38 > 0:27:43caught up with the forgotten observations Berthold had made.
0:27:43 > 0:27:49His work on cockerels, Horsley and Murray's experiments with thyroid
0:27:49 > 0:27:55glands, George Oliver's discovery of adrenaline, and now Halban.
0:27:55 > 0:27:58All of it came together to give us
0:27:58 > 0:28:02a modern understanding of a separate system of internal secretions
0:28:02 > 0:28:06constantly at work within our bodies.
0:28:07 > 0:28:11All that was now needed was to give these secretions a name.
0:28:14 > 0:28:17The story goes, that at a University dinner in Cambridge,
0:28:17 > 0:28:22Ernest Starling, a leading physiologist of the day,
0:28:22 > 0:28:25coined the term that we have all come to use.
0:28:25 > 0:28:28As Starling sat talking with a colleague,
0:28:28 > 0:28:31they both struggled to find a name for these secretions that
0:28:31 > 0:28:36could pass to another part of the body and stimulate it directly.
0:28:36 > 0:28:41A scholar of Ancient Greek just happened to pass by and
0:28:41 > 0:28:43so they asked him.
0:28:43 > 0:28:46someone said, "Well , they ought to call it something like hormao,"
0:28:46 > 0:28:50which is the Greek word for "I excite" or "stir up".
0:28:50 > 0:28:52And, interestingly, Starling then gave
0:28:52 > 0:28:55a lecture at the Croonian Society,
0:28:55 > 0:28:58and suddenly used the word "hormone".
0:28:58 > 0:29:01Noone had heard it before, and that was it.
0:29:01 > 0:29:05The name stuck and today we've all heard of hormones.
0:29:05 > 0:29:10But you may not realise just how fundamental they are.
0:29:10 > 0:29:13Every form of life that has more than one cell - every plant,
0:29:13 > 0:29:19every animal, from an earthworm to a killer whale uses hormones.
0:29:19 > 0:29:23There are more than 80 known hormones in humans alone,
0:29:23 > 0:29:27and they all have vastly different roles.
0:29:27 > 0:29:29If you're feeling stressed,
0:29:29 > 0:29:32that's one of the stress hormones, cortisol, at work.
0:29:32 > 0:29:36If you're preparing for exercise, adrenaline will kick in,
0:29:36 > 0:29:39that well known "fight-or-flight" hormone.
0:29:39 > 0:29:43Hormones even have a hand in the bonding process.
0:29:43 > 0:29:46That one's oxytocin.
0:29:47 > 0:29:50But what are hormones?
0:29:50 > 0:29:54Well, there are different types - amines, peptides and steroids,
0:29:54 > 0:29:58and every single hormone has a different molecular structure.
0:29:58 > 0:30:02But what unites them is how they work.
0:30:04 > 0:30:08Each hormone is aimed at a particular target cell.
0:30:08 > 0:30:11Strange as it may be, let's imagine I'm a hormone,
0:30:11 > 0:30:13heading for my target.
0:30:13 > 0:30:16Each hormone flows through the bloodstream,
0:30:16 > 0:30:18passing over billions of cells.
0:30:18 > 0:30:21But they will only have their desired effect when they reach
0:30:21 > 0:30:26the right one, a cell that matches their specific chemical structure.
0:30:26 > 0:30:31You see, hormones only work at specific cells.
0:30:31 > 0:30:38Anywhere else, it's like trying to unlock a door with the wrong key.
0:30:38 > 0:30:41'OK, wrong cell - let's try that again.'
0:30:44 > 0:30:49At these specific target cells, the key fits perfectly
0:30:49 > 0:30:54and the hormone effectively unlocks the cell to get it working.
0:30:56 > 0:30:59Once the hormone acts on its target cell,
0:30:59 > 0:31:03it can change the way it behaves to make it perform a specific task.
0:31:05 > 0:31:09For example, when adrenaline reaches the heart, it makes it beat faster.
0:31:10 > 0:31:13Each hormone has its own unique role.
0:31:15 > 0:31:17Hormones have many different actions
0:31:17 > 0:31:20and many different timescales of action.
0:31:20 > 0:31:23So adrenaline has an effect on the heart for only a few
0:31:23 > 0:31:27minutes, whereas oestrogen, secreted every day,
0:31:27 > 0:31:31has effects which last for years.
0:31:31 > 0:31:34Building up over long timescales like this,
0:31:34 > 0:31:38some hormones can have dramatic effects on our body.
0:31:38 > 0:31:43As one of my former patients can help to demonstrate.
0:31:49 > 0:31:51At seven-foot-six,
0:31:51 > 0:31:56this is Chris Greener, one of Britain's tallest men.
0:31:56 > 0:31:59And here he is with our film's director, James,
0:31:59 > 0:32:02who's a good five-foot-nine.
0:32:02 > 0:32:06Chris leads a healthy, if unusual life.
0:32:06 > 0:32:09When people say to me, "What's the problems about being tall?"
0:32:09 > 0:32:11I say, "Oh, well, getting clothes. I have to have everything
0:32:11 > 0:32:13"made-to-measure."
0:32:13 > 0:32:17I've had this problem for, well, the best part of 50 years.
0:32:17 > 0:32:21When I left primary school, I was taller than most of the teachers.
0:32:21 > 0:32:25I just thought I would stop growing, but I didn't.
0:32:25 > 0:32:27HE LAUGHS
0:32:27 > 0:32:31Chris's condition, called acromegalic gigantism,
0:32:31 > 0:32:35we now know is caused by over-production of growth hormone.
0:32:35 > 0:32:36Which meant he kept growing,
0:32:36 > 0:32:40and growing and growing well into his 20s.
0:32:40 > 0:32:42When I started work, I was six-foot-seven.
0:32:42 > 0:32:45when I was named tallest man, I was about seven-foot-five.
0:32:45 > 0:32:48So I grew about ten inches in seven years.
0:32:48 > 0:32:50Some of those years, I was probably growing in excess of two
0:32:50 > 0:32:52inches a year.
0:32:52 > 0:32:56It was by studying people like Chris that the mysterious role
0:32:56 > 0:33:00hormones play in growth was unravelled.
0:33:03 > 0:33:10The story starts in the 1780s, with a man similar in stature to Chris.
0:33:10 > 0:33:14When Irishman Charles Byrne came to London to earn
0:33:14 > 0:33:19a living as a human curiosity, he quickly attracted the
0:33:19 > 0:33:24attention of a notorious scientist and collector called John Hunter.
0:33:24 > 0:33:29Going against Byrne's dying wish to be buried at sea,
0:33:29 > 0:33:36Hunter stole his body and displayed the skeleton in a museum.
0:33:36 > 0:33:38And, as unethical as this was,
0:33:38 > 0:33:42it did leave scientists an invaluable clue.
0:33:42 > 0:33:48More than a century later, in 1909, the brilliant neurosurgeon,
0:33:48 > 0:33:53Harvey Cushing, tried to explain why Byrne had grown so tall.
0:33:53 > 0:33:57He used the skull to suggest that the cause might lie within
0:33:57 > 0:34:00a tiny gland that's hidden at the base of the brain.
0:34:00 > 0:34:03It's called the pituitary and it's incredibly
0:34:03 > 0:34:09difficult to find, as pathologist Dr Suzie Lishman explains.
0:34:09 > 0:34:11This is a human brain,
0:34:11 > 0:34:13and you can see that it is an amazingly complex
0:34:13 > 0:34:17and rich network of nerves controlling all of our movement,
0:34:17 > 0:34:20our sensations, and our higher function.
0:34:20 > 0:34:23So where does the pituitary gland fit into all this?
0:34:23 > 0:34:25Well, it's not quite as easy to see,
0:34:25 > 0:34:30and the only clue we've really got is this very short stalk.
0:34:30 > 0:34:33This is the pituitary stalk and this is where the pituitary gland
0:34:33 > 0:34:36is attached. We had to remove it when we removed the brain.
0:34:36 > 0:34:41Now, if we have a look at the pituitary,
0:34:41 > 0:34:45here it is - a tiny organ, around the size of a baked bean,
0:34:45 > 0:34:48that sits on that stalk at the base of the brain, and I think
0:34:48 > 0:34:52you can just see the stalk, that attaches it to the brain.
0:34:52 > 0:34:54Back in the 1900s,
0:34:54 > 0:34:59Cushing didn't really fully understand what the pituitary did,
0:34:59 > 0:35:03but he was convinced it was important because of where it was.
0:35:05 > 0:35:08And if we look in the base of the skull,
0:35:08 > 0:35:10we can see where the pituitary nestles,
0:35:10 > 0:35:13in this area called the pituitary fossa.
0:35:13 > 0:35:16So it's very carefully protected by a ring of bone to make
0:35:16 > 0:35:18sure that it doesn't get damaged.
0:35:18 > 0:35:20The protective bone layer convinced Cushing
0:35:20 > 0:35:25of the pituitary's importance and that here lay the explanation
0:35:25 > 0:35:28of Charles Byrne's unusual height.
0:35:28 > 0:35:31And that's what's so interesting when Harvey Cushing
0:35:31 > 0:35:33examined the skull of Charles Byrne.
0:35:33 > 0:35:36Instead of having this small, bean-sized area, there was
0:35:36 > 0:35:40a much, much bigger hole and that's because the bone had been
0:35:40 > 0:35:43eroded, and Cushing deduced that that was because he had
0:35:43 > 0:35:48a pituitary adenoma, or tumour, that had grown, forcing the bone away.
0:35:48 > 0:35:51Cushing deduced, correctly as it turns out,
0:35:51 > 0:35:55that Byrne's height was due to this tumour on the pituitary,
0:35:55 > 0:36:00causing it to overproduce a hormone that tells our bodies to grow.
0:36:01 > 0:36:04A similar pituitary tumour had caused Chris Greener's height.
0:36:06 > 0:36:08As with the Irish giant,
0:36:08 > 0:36:12the tumour caused the pituitary to carry on pumping excessive
0:36:12 > 0:36:17quantities of growth hormone long past his teenage years.
0:36:17 > 0:36:20They put it on the machine and pressed the button
0:36:20 > 0:36:22and the needle went "bing", off the end.
0:36:22 > 0:36:27They reckoned I had over 200 growth hormones per unit of blood,
0:36:27 > 0:36:30when the average is about 15, plus or minus a couple.
0:36:30 > 0:36:35Charles Byrne died at the age of 22, with his tumour still untreated.
0:36:35 > 0:36:40But in Chris's case, we were able to destroy his tumour with radiotherapy
0:36:40 > 0:36:46and he stopped growing, and he's still going strong at the age of 70.
0:36:46 > 0:36:49Conditions like Chris' are fascinating.
0:36:49 > 0:36:51Though incredibly rare,
0:36:51 > 0:36:55they serve to emphasise just how important hormones are.
0:36:55 > 0:37:00And, as we shall see, the next breakthrough in our understanding
0:37:00 > 0:37:05of hormones quite literally transformed the lives of millions.
0:37:05 > 0:37:10This is a vial of human insulin. It's a hormone.
0:37:10 > 0:37:13Probably the best-known hormone of them all.
0:37:13 > 0:37:17Without it, you develop diabetes and although that is treatable now,
0:37:17 > 0:37:22before the discovery of insulin, diabetes was a death sentence.
0:37:25 > 0:37:28For children who don't make the hormone, insulin,
0:37:28 > 0:37:31sugar that would otherwise be absorbed as energy,
0:37:31 > 0:37:36passed straight through the body into their urine.
0:37:36 > 0:37:39This is why the disease is called diabetes.
0:37:39 > 0:37:43The most common form, diabetes mellitus, literally means
0:37:43 > 0:37:49"a sweet fountain", because the urine of a sufferer tastes sweet.
0:37:49 > 0:37:53Without the ability to store this vital energy, the child
0:37:53 > 0:38:00slowly wasted away to nothing and never survived beyond their teens.
0:38:00 > 0:38:03It was incredibly difficult to find a cure to diabetes,
0:38:03 > 0:38:06even though there was evidence that one organ in particular,
0:38:06 > 0:38:10the pancreas, might be at the root of it.
0:38:10 > 0:38:14In the late 19th century, a couple of German physiologists
0:38:14 > 0:38:18and clinicians removed the pancreas from dogs,
0:38:18 > 0:38:21and showed that they got diabetes.
0:38:21 > 0:38:27Now, this led the way to identifying the pancreas as the source
0:38:27 > 0:38:33of raising blood sugar levels, that is, becoming diabetic.
0:38:33 > 0:38:37This is a pig's pancreas and it's about the same size
0:38:37 > 0:38:39and shape as a human pancreas, which is
0:38:39 > 0:38:43located in the upper part of the tummy, at the back.
0:38:43 > 0:38:47And it's an amazing organ because it has two main functions.
0:38:47 > 0:38:50One is to produce digestive juices,
0:38:50 > 0:38:54which enter the stomach through the pancreatic duct, there,
0:38:54 > 0:39:00and the other is to produce insulin, which controls sugar levels.
0:39:00 > 0:39:03This presented a problem for anybody who wanted to use
0:39:03 > 0:39:07the pancreas as a potential cure for diabetes.
0:39:07 > 0:39:10The trouble with the pancreas is that, actually, most
0:39:10 > 0:39:16of the pancreas is made up of cells that secrete digestive enzymes.
0:39:16 > 0:39:19So if you'd have just mashed up the pancreas,
0:39:19 > 0:39:22there would've been virtually no insulin in it.
0:39:22 > 0:39:27All it would've been would've been, in fact, digestive juices.
0:39:27 > 0:39:30So, who was the genius to crack this problem
0:39:30 > 0:39:35and earn what was the first Nobel Prize in Endocrinology?
0:39:37 > 0:39:41Frederick Banting was, in fact, the unlikeliest of medical pioneers.
0:39:41 > 0:39:45He certainly didn't hit on his revolutionary cure for diabetes
0:39:45 > 0:39:49while working in a well-funded lab.
0:39:49 > 0:39:53Rather, he was a failing GP in Ontario in Canada.
0:39:56 > 0:39:57He was heavily in debt
0:39:57 > 0:40:01and would subsidise his income by giving lectures to medical students.
0:40:01 > 0:40:05And yet, he was responsible for one of the most sensational
0:40:05 > 0:40:09and dramatic discoveries in the whole of endocrinology.
0:40:10 > 0:40:13During his research for one of these lectures,
0:40:13 > 0:40:16he just happened to come across an article in the little-known
0:40:16 > 0:40:20publication, Surgery, Gynaecology and Obstetrics.
0:40:20 > 0:40:24This referred to the possibility of stopping the digestive
0:40:24 > 0:40:29function of the pancreas, effectively killing off the enzymes,
0:40:29 > 0:40:31and just leaving the hormone-producing cells
0:40:31 > 0:40:34to do their work.
0:40:34 > 0:40:37He spent the day slogging over his notes,
0:40:37 > 0:40:41thinking how the body controls sugar and, in particular,
0:40:41 > 0:40:44how the pancreas deals with it.
0:40:46 > 0:40:49He went to bed with these thoughts still running through his mind,
0:40:49 > 0:40:54and woke, quite suddenly, with a surprising revelation.
0:40:59 > 0:41:02And this was Frederick Banting's "eureka" moment.
0:41:02 > 0:41:06And these are the words of a note he wrote in the middle
0:41:06 > 0:41:09of the night. He said, "Diabetus" - spelled wrong, he was
0:41:09 > 0:41:10an appalling speller, apparently,
0:41:10 > 0:41:12but it was the middle of the night...
0:41:12 > 0:41:15"Ligate the pancreatic ducts of dogs.
0:41:15 > 0:41:21"Keep dogs alive till the acini degenerate leaving the islets.
0:41:21 > 0:41:25"Try to isolate the internal secretion of these to relieve
0:41:25 > 0:41:27"glycosurea".
0:41:27 > 0:41:29You need to be a doctor to understand that,
0:41:29 > 0:41:34but this was the first steps in the cure to diabetes.
0:41:34 > 0:41:37He suddenly thought, "If I tie off the duct that produces all
0:41:37 > 0:41:42"these digestive enzymes from the pancreas, perhaps they might
0:41:42 > 0:41:46"degenerate and I could therefore
0:41:46 > 0:41:50"isolate the few cells, or islets,
0:41:50 > 0:41:56"that produce insulin, and thereby produce an insulin supplement."
0:41:57 > 0:42:00What Banting did was to operate on dogs
0:42:00 > 0:42:04and surgically tie off the pancreatic duct, there.
0:42:04 > 0:42:08He kept them alive for six weeks, and at the end of that time
0:42:08 > 0:42:12the digestive enzyme cells had died, and he was essentially left
0:42:12 > 0:42:16with a pancreas that was just producing insulin.
0:42:16 > 0:42:21Amazingly, when trialled on animals, extract from this dog
0:42:21 > 0:42:27pancreas proved Banting's theory was right, and by January 1922,
0:42:27 > 0:42:34he was ready see whether the same extract would work on humans.
0:42:34 > 0:42:37Leonard Thompson had been a diabetic from a very early age.
0:42:37 > 0:42:40And in 1921, when he was 14,
0:42:40 > 0:42:45he was admitted to Toronto General Hospital, days away from death.
0:42:45 > 0:42:49He looked so thin, some people thought he was a famine victim.
0:42:49 > 0:42:51He was pale, his hair was falling out,
0:42:51 > 0:42:55and he smelled of acetone, characteristic of diabetes.
0:42:55 > 0:42:57And it was that stage that he
0:42:57 > 0:43:01and his father agreed to have Banting's new experimental treatment
0:43:01 > 0:43:08containing insulin, of what was described as "thick, brown muck."
0:43:08 > 0:43:12After a little refinement, this so-called "muck",
0:43:12 > 0:43:15still made from dog's pancreas,
0:43:15 > 0:43:18gave Thompson a whole new lease of life.
0:43:20 > 0:43:22And here's a picture of Leonard Thompson.
0:43:22 > 0:43:25This is after he started treatment with insulin
0:43:25 > 0:43:28and he should have been dead, but happily,
0:43:28 > 0:43:32he was first patient to be successfully treated and it's
0:43:32 > 0:43:36wonderful because I've never seen a picture of Leonard Thompson before.
0:43:36 > 0:43:41Now produced synthetically, insulin has gone on to save
0:43:41 > 0:43:47the lives of millions - by any measure, a complete medical triumph.
0:43:47 > 0:43:51In the 1920s, however, it opened the floodgates to a new wave
0:43:51 > 0:43:56of hormone research, with others hoping to find more miracle cures.
0:43:58 > 0:44:00Sadly, as we have seen before,
0:44:00 > 0:44:04this quest can have very unwelcome consequences.
0:44:04 > 0:44:10After this great success, we go from the sublime to the "cor, blimey".
0:44:10 > 0:44:17Because endocrine science, for a bit, went seriously off track.
0:44:17 > 0:44:20The days of Brown-Sequard may have been long behind us,
0:44:20 > 0:44:24but the hope for a secret to eternal youth remained.
0:44:24 > 0:44:27And with the miraculous survival of Leonard Thompson,
0:44:27 > 0:44:29and other diabetics like him,
0:44:29 > 0:44:33the idea grew that if replacing missing hormones could cure
0:44:33 > 0:44:39the sick, surely increasing normal levels could enhance the healthy.
0:44:42 > 0:44:47Cue one of the most bizarre fads in medical history.
0:44:47 > 0:44:51All across Europe, and indeed the world, men began to subject
0:44:51 > 0:44:54themselves to an operation which was extremely perverse.
0:44:54 > 0:44:57What they wanted to do was to recapture their youth.
0:45:02 > 0:45:08This is the Prater in Vienna - the oldest amusement park in the world.
0:45:08 > 0:45:12Surprisingly, in the early 20th century, it was the site
0:45:12 > 0:45:17of a laboratory which carried out quite remarkable experiments.
0:45:20 > 0:45:24The Biological Research Institute, on the grounds of this park,
0:45:24 > 0:45:28also went by the nickname of "the vivarium",
0:45:28 > 0:45:31and it was here that physiologist Eugen Steinach developed
0:45:31 > 0:45:36a procedure which he claimed could reverse the ageing process.
0:45:39 > 0:45:43This lab was particularly interested in changing the body's
0:45:43 > 0:45:46natural processes.
0:45:49 > 0:45:54Steinach proposed a very similar technique to the one Banting
0:45:54 > 0:45:58had used to obtain insulin in the pancreas, tying off the duct
0:45:58 > 0:46:03from a gland to isolate one particular hormone within.
0:46:03 > 0:46:07This time, however, he wanted to isolate the male hormone
0:46:07 > 0:46:12testosterone and, for that, he had a very different organ in mind.
0:46:12 > 0:46:17Steinach's procedure was to tie off the tube carrying the sperm -
0:46:17 > 0:46:20in modern parlance, a vasectomy.
0:46:20 > 0:46:23What he thought would happen was that this would create more
0:46:23 > 0:46:26room for the hormone-producing cells in the testes,
0:46:26 > 0:46:29and this would give his patients more vigour.
0:46:31 > 0:46:36Hard as it is to believe, "the Steinach" was a sensation,
0:46:36 > 0:46:39with people flocking to have it done on themselves,
0:46:39 > 0:46:43including some rather high-profile patients.
0:46:43 > 0:46:48Among them was the famous poet William Butler Yeats.
0:46:50 > 0:46:55At 69, Yeats was in poor health, and really quite depressed,
0:46:55 > 0:46:58and he had writer's block.
0:46:58 > 0:47:01But, after the procedure,
0:47:01 > 0:47:04he noticed a huge increase in his creative powers,
0:47:04 > 0:47:08as well as his sexual desire.
0:47:08 > 0:47:10Interestingly, some people think Yeats wrote
0:47:10 > 0:47:12some of his best poetry after the procedure.
0:47:15 > 0:47:20'A young man in the dark am I, But a wild old man in the light,
0:47:20 > 0:47:25'Then, said she to that wild old man, His stout stick under his hand
0:47:25 > 0:47:31'Love to give, or to withhold, is not at my command'
0:47:34 > 0:47:36And it wasn't just his poetry.
0:47:36 > 0:47:40A few months after the Steinach, Yeats took up with an actress
0:47:40 > 0:47:45who, at 27, was 42 years younger than him.
0:47:45 > 0:47:50Had Steinach stumbled on the secret of eternal youth?
0:47:54 > 0:47:56Well, of course he hadn't.
0:47:56 > 0:47:59And just as with Brown-Sequard, there was
0:47:59 > 0:48:03no way to reproduce the results he'd claimed.
0:48:03 > 0:48:07We now know that there is no scientific rationale,
0:48:07 > 0:48:10and that it was another scientific blind alley.
0:48:10 > 0:48:16Endocrinology had come a long way by the time we reach Steinach,
0:48:16 > 0:48:20but his procedure failed because his understanding of how hormones
0:48:20 > 0:48:23work was far too simplistic.
0:48:25 > 0:48:28Steinach thought that the more testosterone there was
0:48:28 > 0:48:33circulating around the body, the more invigorated you became.
0:48:33 > 0:48:36But the problem was, it wasn't that simple.
0:48:36 > 0:48:41First, Steinach was wrong to think that tying off the sperm
0:48:41 > 0:48:45ducts caused an increase of the male sex hormone testosterone.
0:48:45 > 0:48:49But, more crucially, even if he could have raised its levels,
0:48:49 > 0:48:53he completely misjudged what would happen.
0:48:53 > 0:48:55There's only one part of the endocrine system
0:48:55 > 0:49:00he hadn't understood and that's the most important part of all.
0:49:01 > 0:49:06Steinach had no idea how hormones are regulated.
0:49:06 > 0:49:10But the publicity around his claims spurred on a huge
0:49:10 > 0:49:11amount of research,
0:49:11 > 0:49:15and out of this came an explanation of where he'd gone wrong.
0:49:16 > 0:49:19And, more than this, it gave a new understanding of a key
0:49:19 > 0:49:25role of a tiny gland we've met before - the pituitary.
0:49:28 > 0:49:30As well as producing growth hormone,
0:49:30 > 0:49:34the pituitary has the crucial job of ensuring that the
0:49:34 > 0:49:38levels of many hormones never get too high or too low.
0:49:39 > 0:49:44And that's why Steinach's technique couldn't possible have worked.
0:49:44 > 0:49:47Even if you overload the endocrine system with testosterone,
0:49:47 > 0:49:51normally the pituitary will step in to bring the levels
0:49:51 > 0:49:53back down again to normal.
0:49:56 > 0:50:01In many ways, the pituitary works just like a household thermostat.
0:50:01 > 0:50:04It can sense if hormone levels have gone wrong
0:50:04 > 0:50:07and send messages to some of the major glands, getting them
0:50:07 > 0:50:11to produce more or less hormone as needed.
0:50:12 > 0:50:15The discovery of this aspect of the pituitary was a real
0:50:15 > 0:50:18milestone in my field.
0:50:18 > 0:50:21Even when I was a medical student in the '60s,
0:50:21 > 0:50:26this tiny gland was still considered the lynchpin to hormone regulation.
0:50:28 > 0:50:32But what I love about this story is it never stands still.
0:50:32 > 0:50:37And even in the last few years, research has uncovered an entirely
0:50:37 > 0:50:41new system of regulation, which has led us to broaden our views.
0:50:43 > 0:50:47In fact, this new system is challenging our perceptions of not
0:50:47 > 0:50:52only how we control hormones but, indeed, how hormones control us.
0:50:58 > 0:51:02Professor Sadaf Farooqi has been working at the cutting edge
0:51:02 > 0:51:06of hormone research for more than a decade.
0:51:06 > 0:51:10She and her team have been studying the role of hormones in obesity.
0:51:10 > 0:51:16And in this condition, hormones work in a much more surprising way
0:51:16 > 0:51:18than we ever imagined.
0:51:18 > 0:51:20So the first real breakthrough emerged with
0:51:20 > 0:51:23the discovery of a completely new hormone called leptin,
0:51:23 > 0:51:27which was first found in mice which were severely obese.
0:51:27 > 0:51:31And this really paved the way for finding out an entirely new
0:51:31 > 0:51:33system for how weight is regulated.
0:51:33 > 0:51:36And this system depends on the hormone leptin, which is
0:51:36 > 0:51:38actually made by our fat.
0:51:38 > 0:51:42It was a discovery that was entirely unprecedented - a hormone
0:51:42 > 0:51:47produced not by a gland, but by cells which no-one thought
0:51:47 > 0:51:50had any part in the endocrine system.
0:51:52 > 0:51:55And this is something we had not realised before.
0:51:55 > 0:51:57We didn't know that fat could make hormones. We knew that fat
0:51:57 > 0:52:01is there to store extra calories, but this was a really important
0:52:01 > 0:52:05discovery because we learnt that fat could make a hormone that circulated
0:52:05 > 0:52:09in the bloodstream and acted on the brain to control our weight.
0:52:09 > 0:52:15Incredibly, with this hormone, our fat cells themselves can control
0:52:15 > 0:52:21how much we eat by setting up their own feedback loop with the brain.
0:52:21 > 0:52:23It works like this.
0:52:23 > 0:52:28Leptin is constantly being produced by our fat cells, and the more
0:52:28 > 0:52:32fat stores we have in general, the more leptin flows in the blood.
0:52:32 > 0:52:36This essentially tells our brain that we've eaten enough
0:52:36 > 0:52:38and we lose our appetite.
0:52:38 > 0:52:43But where Sadaf's work comes in is when this system doesn't work
0:52:43 > 0:52:47properly, and, for some reason, the fat cells don't make leptin.
0:52:50 > 0:52:55Sadaf is still working to understand all the reasons behind how
0:52:55 > 0:53:00this can happen, but by figuring out one cause in particular,
0:53:00 > 0:53:03she has already made a fantastic discovery.
0:53:03 > 0:53:08Remarkably, a patient's inability to produce leptin can,
0:53:08 > 0:53:12in some cases, come down to their genes.
0:53:13 > 0:53:17A key part of how we discovered the role of the hormone leptin
0:53:17 > 0:53:21was using genetics, and we were able to look at the DNA of patients
0:53:21 > 0:53:25and find that they had a mutation or a gene defect that was
0:53:25 > 0:53:27disrupting the hormone leptin.
0:53:27 > 0:53:29And this was the cause of their weight problem.
0:53:29 > 0:53:33In the rare case that someone has this faulty gene, they will be
0:53:33 > 0:53:37unable to control their appetite and so will eat more than their
0:53:37 > 0:53:41body needs and this will inevitably mean that they become obese.
0:53:41 > 0:53:45Up until that time, most people thought that actually
0:53:45 > 0:53:49your tendency to gain weight was purely down to self-control.
0:53:49 > 0:53:52It was purely down to the food you eat and the exercise you do,
0:53:52 > 0:53:55and there wasn't really any biology involved.
0:53:55 > 0:53:58Actually what we showed through the discovery of leptin
0:53:58 > 0:54:01and its lacking in patients is that, in fact, genes can play
0:54:01 > 0:54:05an important role in controlling our weight, and they do
0:54:05 > 0:54:06so by affecting our appetite,
0:54:06 > 0:54:10and leptin is a key regulator of appetite.
0:54:10 > 0:54:14It's an incredible discovery - that hormones are a key
0:54:14 > 0:54:17factor in our ability to maintain a healthy weight.
0:54:20 > 0:54:24And the fact that even a person's appetite can be marshalled
0:54:24 > 0:54:30by a hormone has given people new hope in the battle against obesity.
0:54:30 > 0:54:33That really meant that we can find treatments for those patients.
0:54:33 > 0:54:36And we were able to give them leptin back,
0:54:36 > 0:54:39and we did that by giving them injections, which they take
0:54:39 > 0:54:42twice a day, and, thankfully, it's worked incredibly well and now they
0:54:42 > 0:54:45live entirely normal lives, they are a normal weight, and many of
0:54:45 > 0:54:48the other health problems that they suffered with have been corrected.
0:54:50 > 0:54:53With the simple introduction of leptin, Sadaf has been able
0:54:53 > 0:54:57to effectively cure obesity in those patients who would
0:54:57 > 0:55:01otherwise have no control over their weight.
0:55:01 > 0:55:05It's a striking example of the power of hormones.
0:55:05 > 0:55:08And, alongside other recent breakthroughs,
0:55:08 > 0:55:12it suggests that we are on the verge of discovering a whole range
0:55:12 > 0:55:17of new hormones with potentially breathtaking capabilities.
0:55:19 > 0:55:20Well, it's fascinating, really,
0:55:20 > 0:55:23because we've come from understanding
0:55:23 > 0:55:26what the classical endocrine glands were, that is
0:55:26 > 0:55:31from Brown-Sequard and everyone mashing up a few glands,
0:55:31 > 0:55:35to realising that, actually, most of our body now produces hormones,
0:55:35 > 0:55:38and I think in the future the discovery of new
0:55:38 > 0:55:42hormones is going to be absolutely vast.
0:55:45 > 0:55:48Work like Sadaf's forces us to reassess
0:55:48 > 0:55:54whether what we do is down to free will or simply our hormones.
0:55:54 > 0:55:58And it's a heady thought to think that, one day, we might harness the
0:55:58 > 0:56:04power of these chemicals to control almost every aspect of our biology.
0:56:05 > 0:56:09But there are lessons to be learned from the history of hormones.
0:56:09 > 0:56:14Stories like oophorectomies and the search for eternal youth remind us
0:56:14 > 0:56:18that a little bit of knowledge is a decidedly dangerous thing.
0:56:19 > 0:56:23Even now, we mustn't assume that we have all the answers.
0:56:23 > 0:56:26As soon as we think we understand hormones completely,
0:56:26 > 0:56:32a new discovery will come along and prove just how little we know.
0:56:32 > 0:56:36It's extraordinary that the study of hormones is only just over
0:56:36 > 0:56:38100 years old.
0:56:38 > 0:56:41There have been amazing discoveries
0:56:41 > 0:56:46and yet it's a science that is in its infancy.
0:56:46 > 0:56:51And, for me, the ongoing fascination is that it's going to be
0:56:51 > 0:56:56many years before hormones reveal all their secrets.