0:00:05 > 0:00:07In 1815, with Europe at war,
0:00:07 > 0:00:12four young Germans decided to do a particularly foolhardy experiment.
0:00:12 > 0:00:16One which would transform their lives and ours, as well.
0:00:18 > 0:00:22One of them, a pharmacist, had created some intriguing crystals
0:00:22 > 0:00:24which he carefully measured out.
0:00:26 > 0:00:28He was keen to see what effects they would have on his body.
0:00:30 > 0:00:35He dissolved them in alcohol and then diluted it with water.
0:00:35 > 0:00:38Since the crystals had recently been made
0:00:38 > 0:00:40and only previously tested on dogs,
0:00:40 > 0:00:43they had very little idea what was going to happen.
0:00:46 > 0:00:50The answer was, not much. So they did it again.
0:00:55 > 0:00:56Prost!
0:00:58 > 0:00:59Ah!
0:00:59 > 0:01:02This time, there was a pounding headache,
0:01:02 > 0:01:05nausea and extreme flushing.
0:01:05 > 0:01:09So, naturally, they decided to go even more extreme.
0:01:09 > 0:01:12They put the crystals directly on their tongues
0:01:12 > 0:01:15and washed them down with another shot of alcohol.
0:01:19 > 0:01:21Their leader, Friedrich Serturner,
0:01:21 > 0:01:24described falling to the ground semiconscious.
0:01:24 > 0:01:30In terrible pain and fingers twitching with every heartbeat.
0:01:30 > 0:01:32Somehow, he managed to crawl his way
0:01:32 > 0:01:36over to a bottle of really strong vinegar.
0:01:36 > 0:01:38He swallowed it down and the rest,
0:01:38 > 0:01:42he poured into the mouths of his unconscious assistants.
0:01:42 > 0:01:44They were all violently sick.
0:01:46 > 0:01:49Serturner had saved their lives by making them vomit,
0:01:49 > 0:01:51but he noted that for the next few days,
0:01:51 > 0:01:57they continued feeling ill. Aches, sickness and constipation.
0:01:57 > 0:02:02Swallowing the crystals had produced classic symptoms of opium overdose.
0:02:02 > 0:02:04Serturner was thrilled.
0:02:04 > 0:02:08He was the first person ever to extract the essence of opium.
0:02:08 > 0:02:11A white powder that he called morphium.
0:02:11 > 0:02:14He had given birth to a whole new science
0:02:14 > 0:02:18and opened a Pandora's box of good and evil.
0:02:20 > 0:02:24This series tells the extraordinary story of what Serturner unleashed.
0:02:25 > 0:02:28The remarkable medicines which today protect us
0:02:28 > 0:02:30against devastating disease.
0:02:31 > 0:02:35Just over there is a monster of biblical proportions.
0:02:35 > 0:02:37The smallpox virus.
0:02:38 > 0:02:42And the agonies of mortal life.
0:02:43 > 0:02:46I have here a big lump of raw opium.
0:02:46 > 0:02:48You almost want to lick it.
0:02:49 > 0:02:52Drugs that can be terrifyingly lethal.
0:02:52 > 0:02:55This is THE most poisonous substance known to man.
0:02:58 > 0:03:00Or incredibly pleasurable.
0:03:02 > 0:03:04Ooo, yes!
0:03:04 > 0:03:06Blimey, wow!
0:03:06 > 0:03:07HE LAUGHS
0:03:11 > 0:03:15It's a story of two centuries of greed, luck and genius.
0:03:16 > 0:03:19In this programme, I'm going to be telling the remarkable
0:03:19 > 0:03:22stories of the men who abolished pain.
0:03:22 > 0:03:26And by doing so created the world's most popular, desirable
0:03:26 > 0:03:27and addictive drugs.
0:03:45 > 0:03:49This is such an odd and unnatural thing to do.
0:03:49 > 0:03:52I'm not sure I'm going to be able to do it, but let's see.
0:03:52 > 0:03:53POUNDING HEARTBEAT
0:04:02 > 0:04:03OK.
0:04:05 > 0:04:10Argh! Cor! That is just absolutely horrible!
0:04:10 > 0:04:12I'm pushing a needle right through my hand.
0:04:12 > 0:04:16I don't know if it's got through the other end. Sticking out there.
0:04:16 > 0:04:17Ah!
0:04:17 > 0:04:19This is only possible
0:04:19 > 0:04:22because my hand has been numbed with local anaesthetic.
0:04:22 > 0:04:25The fact that I can do that is a testimony,
0:04:25 > 0:04:27if you like, to modern medicine.
0:04:27 > 0:04:30200 years ago, we had almost nothing.
0:04:30 > 0:04:32We had a few herbal medicines.
0:04:32 > 0:04:34If you were having your teeth pulled out or your leg cut off,
0:04:34 > 0:04:37then you were going to be in an awful lot of pain.
0:04:37 > 0:04:40Pain is such a visceral thing that it's not surprising
0:04:40 > 0:04:43that the quest to find a way to control it
0:04:43 > 0:04:47has been such a driving force in the history of drugs.
0:04:52 > 0:04:54For centuries, there was only one substance
0:04:54 > 0:04:58that could reliably relieve pain. Opium.
0:04:59 > 0:05:01A resin extracted from poppies,
0:05:01 > 0:05:04it is one of mankind's oldest and most addictive drugs.
0:05:05 > 0:05:11Yet opium would give rise to today's giant pharmaceutical industry.
0:05:11 > 0:05:12Opium's always been popular.
0:05:12 > 0:05:15It's always been very easy to tell what opium does
0:05:15 > 0:05:19because it acts in a very obvious way. It acts very quickly.
0:05:19 > 0:05:22The Sumerians called it the Joy Plant.
0:05:23 > 0:05:25By the beginning of the 19th century,
0:05:25 > 0:05:27opium was widely available in Europe.
0:05:27 > 0:05:31It was particularly popular when dissolved in alcohol,
0:05:31 > 0:05:33as a medicine called laudanum.
0:05:35 > 0:05:39The trouble is, the raw material was expensive and it was unreliable.
0:05:39 > 0:05:42So no wonder pharmacists began to ask themselves,
0:05:42 > 0:05:47"What exactly is in opium that gives it its seemingly-magical qualities?"
0:05:48 > 0:05:50One of those pharmacists was
0:05:50 > 0:05:53the 20-year-old German Friedrich Serturner,
0:05:53 > 0:05:57whose attempts to produce morphium nearly ended in his death
0:05:57 > 0:06:00and the death of all his assistants.
0:06:00 > 0:06:03His experiments would unlock the key, not just to pain relief,
0:06:03 > 0:06:04but to all modern medicines.
0:06:07 > 0:06:11It took Serturner two years of trial and painful error
0:06:11 > 0:06:15before he discovered how to extract morphium from opium resin.
0:06:15 > 0:06:18I'm hoping to do it in rather less time than that.
0:06:18 > 0:06:20But because morphium is now a Class A drug,
0:06:20 > 0:06:24I'm going to have to do it in a licensed premises.
0:06:29 > 0:06:32Serturner would have started with raw opium
0:06:32 > 0:06:35which comes from the sap of the poppy.
0:06:35 > 0:06:38Now, I have an enormous great block of the stuff here.
0:06:40 > 0:06:43It still smells sort of yeasty.
0:06:45 > 0:06:47Time to extract morphium.
0:06:50 > 0:06:55First, Serturner added a standard solvent. Alcohol.
0:06:55 > 0:06:59The alcohol should already be beginning to extract
0:06:59 > 0:07:01the chemicals from the raw opium.
0:07:01 > 0:07:03This, in essence, is laudanum.
0:07:03 > 0:07:06A sort of tonic they used in the 19th century.
0:07:06 > 0:07:08They gave it to squawking babies.
0:07:14 > 0:07:17One of the ideas which actually comes from alchemy
0:07:17 > 0:07:20is the idea that there might be some active principle.
0:07:20 > 0:07:23Something that lay at the heart of your substance
0:07:23 > 0:07:25which gave it its power.
0:07:25 > 0:07:28And from there, it's actually not a huge step to say,
0:07:28 > 0:07:32what if we take away the alcohol, what are we left with?
0:07:32 > 0:07:35Are we left with that fundamental principle?
0:07:39 > 0:07:43The first thing he extracted was a substance that was acidic.
0:07:45 > 0:07:49He tried it on dogs and absolutely nothing happened.
0:07:51 > 0:07:54Instead of giving up, Serturner tried doing something
0:07:54 > 0:07:56no-one else had previously attempted.
0:07:56 > 0:08:00The received wisdom was the only really important
0:08:00 > 0:08:03chemicals in plants were sharp-tasting acids.
0:08:03 > 0:08:07But Serturner decided to see if he could extract an alkaline chemical,
0:08:07 > 0:08:10the opposite of an acid, from opium.
0:08:10 > 0:08:13He was exploring the unknown.
0:08:13 > 0:08:15When you actually try and do it with modern equipment,
0:08:15 > 0:08:19it gives you a huge respect for what they were doing back then.
0:08:19 > 0:08:21Because every stage would last weeks
0:08:21 > 0:08:25and he obviously had no real idea what he was doing.
0:08:29 > 0:08:34Finally, around 1803, he got this sludgy precipitate.
0:08:37 > 0:08:40From this very unpromising substance,
0:08:40 > 0:08:43Serturner managed to extract some white crystals.
0:08:43 > 0:08:44When he gave these to a dog,
0:08:44 > 0:08:49the dog became sleepy, trembled and then died.
0:08:50 > 0:08:52Serturner was absolutely thrilled.
0:08:52 > 0:08:56He published and sat back, waiting for the applause.
0:08:56 > 0:08:58Which never came.
0:08:58 > 0:09:00It seems people just weren't that interested
0:09:00 > 0:09:05in the workings of a young man doing his bit in a small back room.
0:09:07 > 0:09:09It was not until 10 years later,
0:09:09 > 0:09:13when Serturner purified and took the morphium himself,
0:09:13 > 0:09:15with his three assistants,
0:09:15 > 0:09:17that his dramatic discovery
0:09:17 > 0:09:20finally caught the attention of early chemists.
0:09:24 > 0:09:27Gay-Lussac, who was a doyenne of chemistry in Paris,
0:09:27 > 0:09:30probably the greatest chemist in the world of his day,
0:09:30 > 0:09:34he decided that this paper that had been brought to his attention
0:09:34 > 0:09:38should be translated into French and published.
0:09:38 > 0:09:40And, therefore, it went around the world.
0:09:40 > 0:09:44And the world knew about this isolation. That was so important.
0:09:44 > 0:09:48In extracting the active ingredient of opium,
0:09:48 > 0:09:51Serturner had launched a new age of discovery.
0:09:53 > 0:09:55He had shown that the powers of herbal remedies
0:09:55 > 0:09:58could be captured in a chemical form,
0:09:58 > 0:10:01measured out and quantified as a dose.
0:10:02 > 0:10:05He had also revealed a whole new world
0:10:05 > 0:10:09of previously-unsuspected chemicals hiding in plants.
0:10:09 > 0:10:13They were to become our first real medicines.
0:10:13 > 0:10:16They decided to call these new chemicals
0:10:16 > 0:10:19they were getting out of plants the alkaloids.
0:10:19 > 0:10:23They also decided to give them the name "-ine" at the end.
0:10:23 > 0:10:26And, so, Serturner's white powder
0:10:26 > 0:10:30became not "morphium", but "morphine".
0:10:35 > 0:10:41The isolation of morphine was the single most important event
0:10:41 > 0:10:43that has ever occurred in drug discovery.
0:10:43 > 0:10:46Far more important than the introduction of penicillin
0:10:46 > 0:10:50in terms of advancing the science.
0:10:54 > 0:10:55The extraction of morphine
0:10:55 > 0:10:58was such a big moment in the history of medicine
0:10:58 > 0:11:00because once you had the pure chemical,
0:11:00 > 0:11:03you could give it in a controlled and measured dose.
0:11:03 > 0:11:05You were no longer dependent on the vagaries
0:11:05 > 0:11:07of whatever plant you happened to be eating.
0:11:07 > 0:11:12It also meant they could extract dozens of different alkaloids.
0:11:13 > 0:11:17Nature's medicine cabinet was flung wide open.
0:11:17 > 0:11:19It turned out that alkaloids are the reason
0:11:19 > 0:11:22why many herbal remedies are effective.
0:11:23 > 0:11:26Being the plant's own defence against herbivores,
0:11:26 > 0:11:29a lot were bitter-tasting and poisonous.
0:11:29 > 0:11:31But once isolated, we could start to use them.
0:11:31 > 0:11:33And not just as painkillers.
0:11:35 > 0:11:40Now, I have here my favourite drug of abuse. Caffeine.
0:11:40 > 0:11:44Other famous alkaloids include nicotine
0:11:44 > 0:11:47and the malaria drug, quinine.
0:11:47 > 0:11:49And here's another I take from time to time.
0:11:50 > 0:11:53Codeine was another powerful painkiller
0:11:53 > 0:11:55which was extracted from the poppy.
0:11:55 > 0:11:56Codeine, like morphine,
0:11:56 > 0:12:01works by modulating the way that the brain perceives pain.
0:12:01 > 0:12:05Surprisingly, we are only now beginning to understand
0:12:05 > 0:12:08how these so-called opiate drugs work.
0:12:08 > 0:12:11Normally, raw nerve endings trigger an electrical signal
0:12:11 > 0:12:13which travels to the spine.
0:12:13 > 0:12:16There, it's converted into a chemical signal
0:12:16 > 0:12:17which crosses into other nerves
0:12:17 > 0:12:20which then transmit the message to the brain.
0:12:22 > 0:12:25Once your brain has received that pain message,
0:12:25 > 0:12:30it can decide to tone it down or, indeed, switch it off entirely.
0:12:30 > 0:12:33It does that via another set of nerves
0:12:33 > 0:12:35that send a signal down the spine.
0:12:35 > 0:12:38And that interrupts the incoming pain message.
0:12:40 > 0:12:43Our brains typically activate this pain-relieving pathway
0:12:43 > 0:12:45in times of extreme stress.
0:12:46 > 0:12:49There are a number of different points along the pain pathway
0:12:49 > 0:12:53where you can turn the pain response down.
0:12:53 > 0:12:56And the opiates interact with quite a few of them.
0:12:57 > 0:13:00For example, they make the brain switch on
0:13:00 > 0:13:03the pain-blocking pathways I've just described.
0:13:03 > 0:13:05They also act in the brain
0:13:05 > 0:13:08to reduce the impact of any pain messages that get through.
0:13:08 > 0:13:10There's even recent evidence
0:13:10 > 0:13:15they can dull the raw nerve endings at the site of pain.
0:13:15 > 0:13:17It's no wonder they're so effective.
0:13:20 > 0:13:22The opiates are wonderful painkillers,
0:13:22 > 0:13:25but they do have significant side effects.
0:13:25 > 0:13:28Constipation, vomiting,
0:13:28 > 0:13:32addiction, and if they depress your breathing, death.
0:13:36 > 0:13:40Plants from all over the world were soon being examined
0:13:40 > 0:13:43for alkaloids that might rival the opiates.
0:13:43 > 0:13:47One plant from South America did indeed contain a substance
0:13:47 > 0:13:50with extraordinary pain-killing properties.
0:13:50 > 0:13:53But, like morphine, it came with a heavy price.
0:13:56 > 0:14:01This white powder is an alkaloid extracted from these leaves.
0:14:01 > 0:14:04And these are the coca leaves.
0:14:04 > 0:14:07They're a well-known stimulant in South America.
0:14:07 > 0:14:12Which means that this is coca-ine.
0:14:12 > 0:14:14Better known as cocaine.
0:14:15 > 0:14:20Cocaine was added to wines, which were promoted by the Pope.
0:14:20 > 0:14:24Soft drinks, for those who disapproved of alcohol,
0:14:24 > 0:14:26and soothing drops and lozenges.
0:14:26 > 0:14:31But it was cocaine's reputation for combating hunger and fatigue
0:14:31 > 0:14:35that led a curious Austrian doctor called Sigmund Freud
0:14:35 > 0:14:38to investigate its effects further.
0:14:38 > 0:14:41Sigmund Freud was then a neurologist in Vienna.
0:14:41 > 0:14:44This was well before he developed psychoanalysis.
0:14:44 > 0:14:47And he got extremely interested in cocaine,
0:14:47 > 0:14:49which he called a magical drug,
0:14:49 > 0:14:53which he prescribed to his patients for a whole range of ailments,
0:14:53 > 0:14:56including, ironically enough, morphine addiction.
0:14:56 > 0:15:00He sent samples of cocaine to a number of his colleagues,
0:15:00 > 0:15:04including a trainee eye surgeon called Karl Koller.
0:15:07 > 0:15:09Koller had been using morphine and other substances
0:15:09 > 0:15:14to try and alleviate the searing agony of eye surgery.
0:15:14 > 0:15:15But nothing had worked.
0:15:17 > 0:15:19Koller tasted some cocaine
0:15:19 > 0:15:23and he noticed that the tip of his tongue went numb.
0:15:23 > 0:15:25And he thought to himself, "That's interesting.
0:15:25 > 0:15:28"What would happen if I put cocaine into my eye?"
0:15:28 > 0:15:31Well, he tried it out on a frog and a dog
0:15:31 > 0:15:32and they seemed to be fine,
0:15:32 > 0:15:36so he then decided to try it out on himself.
0:15:36 > 0:15:38What he did, he and a colleague,
0:15:38 > 0:15:41is they got cocaine dissolved in water
0:15:41 > 0:15:44and they dripped some into their eyes...
0:15:46 > 0:15:48Oh, that stings a bit.
0:15:48 > 0:15:53And then they got a nice sharp pin
0:15:53 > 0:15:57and they sort of stabbed their own eyes.
0:15:57 > 0:16:00Now, I'm not going to do that, it sounds insanely dangerous.
0:16:00 > 0:16:01I'm going to use this instead.
0:16:05 > 0:16:08Oh, that's weird. I could just about see it bend then.
0:16:10 > 0:16:11Totally numb.
0:16:13 > 0:16:15This was extraordinary.
0:16:15 > 0:16:17Whereas the opiates numbed pain,
0:16:17 > 0:16:20cocaine is what we now call an anaesthetic,
0:16:20 > 0:16:22which literally means, without sensation.
0:16:24 > 0:16:27Cocaine stops nerves from firing, from sending signals.
0:16:27 > 0:16:30And affects not just the pain-detecting nerves,
0:16:30 > 0:16:31but all of them.
0:16:31 > 0:16:35Which is why it makes the eye or tongue feel completely numb.
0:16:36 > 0:16:39Cocaine made complicated eye surgery possible.
0:16:41 > 0:16:43This stomach-churning footage from 1917
0:16:43 > 0:16:45shows a cataract operation
0:16:45 > 0:16:48performed after putting in a few drops of cocaine.
0:16:49 > 0:16:52It would once have been attempted without pain relief.
0:16:53 > 0:16:56When cocaine gets to the blood and to the brain,
0:16:56 > 0:16:58there it acts very like the opiates.
0:16:58 > 0:17:01And that means it can be a drug of abuse.
0:17:01 > 0:17:05It's not very much used these days, but its derivates certainly are.
0:17:05 > 0:17:07They form the basis of many local anaesthetics.
0:17:07 > 0:17:10And as somebody who's had their teeth drilled
0:17:10 > 0:17:12more times than I care to remember,
0:17:12 > 0:17:15I'm hugely grateful to Dr Koller.
0:17:15 > 0:17:18Or Coca Koller, as he was sometimes called.
0:17:21 > 0:17:25But plants could not provide the level of general anaesthesia
0:17:25 > 0:17:28required to make extensive pain-free surgery possible.
0:17:29 > 0:17:33In the good old days, patients weren't even allowed opium
0:17:33 > 0:17:35because pain was thought to be good for you.
0:17:37 > 0:17:43Pain was understood as an essential component in terms of surgery.
0:17:43 > 0:17:47So although surgeons were concerned about the effects of pain
0:17:47 > 0:17:50on patients in terms of bearability,
0:17:50 > 0:17:55in terms of keeping a patient alive during an operation,
0:17:55 > 0:17:59it was regarded as part of the package.
0:17:59 > 0:18:01The world where surgeons in frockcoats
0:18:01 > 0:18:04committed acts of unspeakable horror
0:18:04 > 0:18:07would be changed by a dentist's chance discovery.
0:18:08 > 0:18:11But it was a breakthrough that was a long time coming.
0:18:11 > 0:18:14Throughout the 18th century, chemists had been experimenting
0:18:14 > 0:18:19with everything they could lay their hands on, from plants to rocks.
0:18:19 > 0:18:21They were particularly interested in creating gasses.
0:18:22 > 0:18:24One of the gasses they produced,
0:18:24 > 0:18:27they did by heating up ammonium nitrate.
0:18:27 > 0:18:31Now, this gas was said to be incredibly poisonous.
0:18:32 > 0:18:35So, surprising that a young chemist called Humphry Davy
0:18:35 > 0:18:39was so keen not just to collect it, but also inhale it.
0:18:43 > 0:18:44It's very hard, I think,
0:18:44 > 0:18:49to get back into the heads of an 18th or 19th-century chemist.
0:18:49 > 0:18:51And that's partly because
0:18:51 > 0:18:54there was so much self-experimentation that went on.
0:18:54 > 0:18:58Now, gasses, you inhaled them,
0:18:58 > 0:19:00and these "airs", as they're called,
0:19:00 > 0:19:05were at one point regarded as possibly panaceas,
0:19:05 > 0:19:08solutions for big medical problems.
0:19:08 > 0:19:11And the way in which they tested them was on themselves.
0:19:12 > 0:19:15The young Humphry Davy was desperate to make his name,
0:19:15 > 0:19:17which is probably why, despite the risks,
0:19:17 > 0:19:20he experimented with this new, potentially-lethal gas.
0:19:22 > 0:19:25It was a foolhardy thing to do.
0:19:25 > 0:19:28I'm doing it under carefully-controlled conditions.
0:19:28 > 0:19:29Ooo!
0:19:29 > 0:19:32Nothing yet. Ho! Huh! OK.
0:19:32 > 0:19:36Now, he records...in his diaries
0:19:36 > 0:19:38that he started off feeling
0:19:38 > 0:19:41sort of sleepy and splenic.
0:19:41 > 0:19:44But after a couple of... Oooh! ..blasts of it,
0:19:44 > 0:19:47he started to want to dance around the room.
0:19:47 > 0:19:48Ooo, yes, I'm feeling it now. Yes.
0:19:48 > 0:19:50Huh! Light-headed.
0:19:56 > 0:19:57HE LAUGHS
0:19:57 > 0:19:59Yep, I can see why they call it laughing gas.
0:20:00 > 0:20:03He also wrote other things...
0:20:03 > 0:20:05which I've entirely forgotten now.
0:20:05 > 0:20:07Er...his notebooks.
0:20:07 > 0:20:10Yes, he was writing something about... Oooh, yeah! So it goes...
0:20:10 > 0:20:13Now, one of the things he noticed and wrote about,
0:20:13 > 0:20:15not in his notebooks, later,
0:20:15 > 0:20:19is its effects on pain, that apparently it reduced it.
0:20:19 > 0:20:22Ooo! Yeah. That's actually all right.
0:20:22 > 0:20:24HE LAUGHS
0:20:27 > 0:20:31Davy published his discovery that nitrous oxide relieved pain
0:20:31 > 0:20:34and even stated its potential in surgery.
0:20:35 > 0:20:38And yet, tragically, he did nothing more about it.
0:20:40 > 0:20:41For the next few decades,
0:20:41 > 0:20:44surgeons went on operating on fully-conscious patients
0:20:44 > 0:20:47and nitrous oxide was used mainly as a recreational drug
0:20:47 > 0:20:50for laughing gas parties.
0:20:54 > 0:20:55It was at one of these in America
0:20:55 > 0:21:00that a young dentist called Horace Wells came across the gas
0:21:00 > 0:21:03and saw how effective it was at dulling pain.
0:21:03 > 0:21:06Because his days were spent yanking out teeth,
0:21:06 > 0:21:08it made a deep impression.
0:21:09 > 0:21:13He was horrified by pain. And there was nothing new about that.
0:21:13 > 0:21:16That surgeons, often the most brilliant surgeons,
0:21:16 > 0:21:20were repulsed by what they had to do.
0:21:20 > 0:21:21If you had to operate on someone,
0:21:21 > 0:21:24if you had to cut into them without anaesthetics,
0:21:24 > 0:21:26it was an awful thing.
0:21:26 > 0:21:28They would vomit with fear
0:21:28 > 0:21:31and revulsion prior to doing an operation.
0:21:34 > 0:21:39After experimenting first on himself and then on some patients,
0:21:39 > 0:21:42Wells realised he had stumbled across something truly miraculous.
0:21:42 > 0:21:46A gas that could open the way to pain-free surgery.
0:21:46 > 0:21:50So, he headed to Harvard Medical School in Boston
0:21:50 > 0:21:53to tell the elite surgeons what he had found.
0:21:54 > 0:21:58He invited a former partner of his, William Morton,
0:21:58 > 0:22:01who was also studying at the medical school,
0:22:01 > 0:22:03to accompany him and share his triumph.
0:22:07 > 0:22:09On a cold winter's night in 1845,
0:22:09 > 0:22:13Wells and Morton appeared before a packed audience
0:22:13 > 0:22:16of doctors and medical students.
0:22:16 > 0:22:19One of the medical students had a problem with his teeth,
0:22:19 > 0:22:20so he was summoned forward,
0:22:20 > 0:22:24he was given a good old blast of nitrous oxide
0:22:24 > 0:22:26from a bag that Wells had brought with him
0:22:26 > 0:22:29and then Wells attempted to extract
0:22:29 > 0:22:31his painful tooth with a pair of pliers.
0:22:31 > 0:22:34No-one's entirely clear what happened next,
0:22:34 > 0:22:36but the student made a noise,
0:22:36 > 0:22:39the audience interpreted that as a cry of pain
0:22:39 > 0:22:44and soon, there were hisses and cries of, "Humbug! Humbug!"
0:22:44 > 0:22:47Which was a deadly medical insult.
0:22:47 > 0:22:53Utterly humiliated, Morton and Wells packed their bags and they left.
0:23:02 > 0:23:05No-one had imagined anaesthesia could exist.
0:23:05 > 0:23:07And I think that's why Wells failed
0:23:07 > 0:23:10in his demonstration of nitrous oxide.
0:23:10 > 0:23:13Because they found the very idea that pain was optional,
0:23:13 > 0:23:16that pain could be deleted, erased from the world,
0:23:16 > 0:23:18so intrinsically fraudulent
0:23:18 > 0:23:21that they were predisposed to reach that conclusion.
0:23:23 > 0:23:27Wells was broken by this failure and would later commit suicide.
0:23:27 > 0:23:31But Morton had seen the commercial potential.
0:23:31 > 0:23:34His real motivation for trying to find
0:23:34 > 0:23:36a decent method of pain relief for dental work
0:23:36 > 0:23:40was actually to find a way of expanding his business.
0:23:40 > 0:23:42Because by that stage,
0:23:42 > 0:23:46new technology produced sets of artificial teeth.
0:23:46 > 0:23:49So, rather than just individual teeth,
0:23:49 > 0:23:52a patient could have a whole set fitted.
0:23:52 > 0:23:55But obviously, to have rotten stumps and roots extracted
0:23:55 > 0:23:59without pain relief was extremely painful
0:23:59 > 0:24:02and a lot of patients did not stick it.
0:24:05 > 0:24:08Morton turned his attention to another substance
0:24:08 > 0:24:10doing the rounds at student parties.
0:24:11 > 0:24:14By adding alcohol to sulphuric acid,
0:24:14 > 0:24:16the students produced a volatile liquid
0:24:16 > 0:24:19known as, sweet oil of vitriol.
0:24:19 > 0:24:22When inhaled, it resulted in a very decent high.
0:24:24 > 0:24:25Whoo! This is strong stuff.
0:24:25 > 0:24:27What is coming out of this
0:24:27 > 0:24:31is a vapour or a liquid that we now know as ether.
0:24:35 > 0:24:39Ether was a popular alternative to alcohol for teetotallers.
0:24:39 > 0:24:42It was sometimes used in pain-relieving medicines.
0:24:42 > 0:24:46And it was this pain-killing effect that got Morton interested.
0:24:50 > 0:24:55Morton started out by using a few drops of ether to numb the mouth.
0:24:55 > 0:24:59Then he used quite a lot to knock out a spaniel.
0:24:59 > 0:25:02But what he really needed to do to prove it was safe and effective
0:25:02 > 0:25:04was try it on a human.
0:25:06 > 0:25:08With no other human volunteers to hand,
0:25:08 > 0:25:11Morton decided to try it out on himself.
0:25:11 > 0:25:13He got a handkerchief,
0:25:13 > 0:25:15and applied some ether.
0:25:17 > 0:25:19He looked at his watch.
0:25:19 > 0:25:22And then stuck the handkerchief over his face.
0:25:27 > 0:25:29A few minutes later, he woke up.
0:25:29 > 0:25:31But he was unable to move.
0:25:31 > 0:25:36As he later wrote, "I was terrified that I would die in that position.
0:25:36 > 0:25:38"And the world would laugh at my folly."
0:25:38 > 0:25:42But the world never got a chance because he made a full recovery,
0:25:42 > 0:25:46and he was now very, very keen to try this out on someone else.
0:25:52 > 0:25:56After successful trials on unsuspecting patients,
0:25:56 > 0:25:58Morton returned to Harvard Medical School.
0:26:00 > 0:26:03They agreed that Morton should have a second chance
0:26:03 > 0:26:07to demonstrate pain relief, in the daunting domed surgical theatre
0:26:07 > 0:26:11at Massachusetts General Hospital.
0:26:11 > 0:26:15The date was set for October 16th, 1846 -
0:26:15 > 0:26:17just 16 days' time.
0:26:20 > 0:26:23On that Friday, this room would have been absolutely packed
0:26:23 > 0:26:25with medical folk,
0:26:25 > 0:26:27many of them expecting, and some of them hoping,
0:26:27 > 0:26:31that the uppity dentist would fail. Again.
0:26:33 > 0:26:36An eminent and extremely sceptical surgeon had been
0:26:36 > 0:26:37booked for the operation.
0:26:39 > 0:26:43At 10am, the appointed hour, there was no sign of Morton,
0:26:43 > 0:26:45so the surgeon prepared to operate.
0:26:45 > 0:26:48His patient was a young man with an enormous tumour on his neck.
0:26:48 > 0:26:52He would have been strapped down because he was going to be awake
0:26:52 > 0:26:54and screaming throughout.
0:26:54 > 0:26:59But before the surgeon could apply his scalpel to the quivering flesh,
0:26:59 > 0:27:02Morton came bursting into the room.
0:27:02 > 0:27:04He was carrying this.
0:27:04 > 0:27:08It's an ether inhaler and he'd had it built overnight.
0:27:08 > 0:27:11No time at all to test it so he must have been feeling almost
0:27:11 > 0:27:15as anxious as the patient because he had no idea if it was going to work.
0:27:17 > 0:27:22Filling the inhaler with ether, Morton handed it to the patient.
0:27:22 > 0:27:26He was relying on a complicated and untested system of valves
0:27:26 > 0:27:27to give the right dose.
0:27:28 > 0:27:32His future depended on this test succeeding -
0:27:32 > 0:27:35the Boston surgeons would not give him another chance.
0:27:37 > 0:27:40When the patient reported feeling a little bit groggy,
0:27:40 > 0:27:45Morton took it back, and then he turned to the surgeon and said,
0:27:45 > 0:27:48"Sir, your patient is ready."
0:27:51 > 0:27:54They were used to operating on people who were screaming
0:27:54 > 0:27:57and trying to get off the table.
0:27:57 > 0:27:59So, anything that held you on the table, even if
0:27:59 > 0:28:03you waved your arms and legs around a bit while it was going on,
0:28:03 > 0:28:07that was preferable to you being wide awake.
0:28:07 > 0:28:11So, the surgeon picked up his scalpel and he started to cut.
0:28:11 > 0:28:14From the patient there came not a sound.
0:28:14 > 0:28:18The operation was long and complicated, but also successful.
0:28:18 > 0:28:23At the end, the patient reported that he had felt no more than a scratch.
0:28:23 > 0:28:26This was an extraordinary moment in the history of surgery -
0:28:26 > 0:28:29an operation performed without pain.
0:28:29 > 0:28:33At the end, the surgeon turned to the audience and he said,
0:28:33 > 0:28:35"Gentlemen, THIS is no humbug."
0:28:39 > 0:28:43There's a wonderful letter from a professor at Harvard to Morton
0:28:43 > 0:28:47saying, "Everyone will want a share of your great discovery.
0:28:47 > 0:28:50"I'm not trying to take a share but we do need to give it a name.
0:28:50 > 0:28:53"I would suggest the name 'anaesthesia'.
0:28:53 > 0:28:54"And we need to give it a name
0:28:54 > 0:28:59"because everyone throughout the world, for the rest of human history,
0:28:59 > 0:29:01"will need to talk about what's just happened and what this is."
0:29:06 > 0:29:10News spread about ether around the world within six months,
0:29:10 > 0:29:14which, given the communications network at the time, I think,
0:29:14 > 0:29:17was highly significant.
0:29:17 > 0:29:20What anaesthesia does is act as a bit of a watershed
0:29:20 > 0:29:24and the ripples sort of permeate out through society.
0:29:24 > 0:29:27And there are lots of wider humanitarian movements
0:29:27 > 0:29:32like the anti-slavery movement, the reform of prisons.
0:29:32 > 0:29:34You just get the general sense that patients'
0:29:34 > 0:29:39and social tolerance of pain is decreasing.
0:29:43 > 0:29:48Pain was no longer an expected and tolerated part of everyday life.
0:29:48 > 0:29:51It was now something that could - and should - be minimised.
0:29:54 > 0:29:58In the 50 years since Serturner's isolation of morphine,
0:29:58 > 0:30:02the rush of scientific discoveries had replaced old superstitions
0:30:02 > 0:30:04and beliefs with new knowledge.
0:30:06 > 0:30:09This would set researchers off hunting for pain-killing drugs
0:30:09 > 0:30:12in some very unlikely places.
0:30:16 > 0:30:20By the middle of the 19th century, the mysterious world of herbs
0:30:20 > 0:30:25and tinctures was being replaced by white powders.
0:30:25 > 0:30:28And these, thanks to this invention,
0:30:28 > 0:30:32were in turn being replaced by...
0:30:37 > 0:30:38..tablets.
0:30:38 > 0:30:41We're about to enter the era where chemists could mass-produce
0:30:41 > 0:30:45the sort of painkillers that we now routinely use every day.
0:30:47 > 0:30:50They were also about to create one of the most addictive
0:30:50 > 0:30:52substances known to man.
0:30:52 > 0:30:56And it all began with this stuff.
0:30:56 > 0:30:57Coal tar.
0:30:59 > 0:31:03Coal tar was a waste product of the burgeoning coal/gas industry.
0:31:03 > 0:31:06And, naturally, chemists tried to find profitable uses for it.
0:31:08 > 0:31:12The availability of coal tar suddenly gives you an enormous new
0:31:12 > 0:31:16library of starting materials.
0:31:16 > 0:31:20And by then chemistry was really taking off - the connectivity,
0:31:20 > 0:31:21the structures, were known.
0:31:21 > 0:31:25And it was suddenly realised that you might be able to made
0:31:25 > 0:31:29either the natural parts themselves or things which mimic them.
0:31:29 > 0:31:33That was a tremendous... A real sea change in chemistry.
0:31:36 > 0:31:39This sea change in chemistry started as it was to proceed -
0:31:39 > 0:31:42with a series of mistakes.
0:31:42 > 0:31:46In 1845, an 18-year-old British chemist tried using coal tar
0:31:46 > 0:31:49to make quinine, a malaria drug.
0:31:49 > 0:31:53Instead, he created the first artificial dye, mauve,
0:31:53 > 0:31:55and made a fortune.
0:31:55 > 0:31:57Coal tar was clearly worth studying,
0:31:57 > 0:32:00yet it would take another accident
0:32:00 > 0:32:02to unlock it's pain-killing potential.
0:32:02 > 0:32:06In this case, a giant cock up involving two French doctors,
0:32:06 > 0:32:08Arnold Cahn and Paul Hepp,
0:32:08 > 0:32:12who were working here at the University of Strasbourg.
0:32:12 > 0:32:16They were testing chemicals derived from coal tar,
0:32:16 > 0:32:19which they were testing on patients with intestinal worms.
0:32:21 > 0:32:24Coal tar had been shown to have antiseptic properties
0:32:24 > 0:32:26when used on skin.
0:32:26 > 0:32:29So, naturally enough, they wanted to see what effects
0:32:29 > 0:32:32some of its derivatives had inside the body.
0:32:32 > 0:32:36Fortunately, they had ready supply of patients.
0:32:36 > 0:32:38These were the days when doctors were quite happy to try out
0:32:38 > 0:32:40almost anything on anybody.
0:32:40 > 0:32:45But even, so I'm amazed they managed to get patients to eat this stuff.
0:32:45 > 0:32:47It is incredibly pungent.
0:32:47 > 0:32:52It is naphthalene, the stuff they use these days in mothballs.
0:32:52 > 0:32:54It did no harm to worms.
0:32:54 > 0:32:57But it did seem to have an effect.
0:32:57 > 0:33:00Amazingly enough, one of their patients who had a fever,
0:33:00 > 0:33:04reported that his fever went down after he'd eaten this stuff.
0:33:04 > 0:33:05That was great news.
0:33:05 > 0:33:09Followed soon afterwards by really bad news - there had been a mix up.
0:33:09 > 0:33:12Whatever the patient had been eating, it wasn't naphthalene.
0:33:14 > 0:33:17The pharmacy here had made a terrible mistake with the labelling.
0:33:18 > 0:33:22The patient had actually been a completely unknown chemical.
0:33:25 > 0:33:27It turned out that the chemical that the pharmacist had been
0:33:27 > 0:33:32accidentally dispensing was this one. Acetanilide.
0:33:32 > 0:33:34Now, who knows how it got here,
0:33:34 > 0:33:36but it's actually used in the dye industry.
0:33:36 > 0:33:39But it was a most fortuitous accident.
0:33:41 > 0:33:44They could have killed the man, but instead acid aniline,
0:33:44 > 0:33:47yet another chemical derived from coal tar,
0:33:47 > 0:33:51was quickly marketed as a profitable fever-reducing drug.
0:33:53 > 0:33:58And not surprising Cahn and Hepp went on to make a fortune.
0:33:58 > 0:34:01But the really significant thing about this discovery
0:34:01 > 0:34:03is what happened next, in Germany.
0:34:11 > 0:34:14There was huge demand for the new headache powders,
0:34:14 > 0:34:18and, clearly, a fortune to be made by anyone who could come up with
0:34:18 > 0:34:20an even better drug.
0:34:20 > 0:34:23Well, here at the Bayer Dye Works there was a young
0:34:23 > 0:34:26and ambitious chemist called Carl Duisberg,
0:34:26 > 0:34:28who decided he would give it a go.
0:34:30 > 0:34:35Bayer's cellars were full of coal tar chemicals like acetanilide.
0:34:35 > 0:34:38And Duisberg set out to see which he could convert into drugs.
0:34:40 > 0:34:44His first discovery, called phenacetin, was very successful.
0:34:44 > 0:34:47We now know that, like acetanilide,
0:34:47 > 0:34:50it's converted in the body to paracetamol.
0:34:52 > 0:34:55Bayer's factory here grew rapidly on the profits.
0:34:55 > 0:34:57And so did their ambitions.
0:34:58 > 0:35:03Another substance they got really interested in was salicylic acid.
0:35:03 > 0:35:05Now, because it's derived from coal tar,
0:35:05 > 0:35:08they thought originally maybe it's an antiseptic.
0:35:08 > 0:35:11They rubbed it on the skin and swallowed it.
0:35:11 > 0:35:15Unfortunately, it didn't kill bugs like typhoid.
0:35:15 > 0:35:18But what it did do, if you had a fever, is it brought it down.
0:35:18 > 0:35:21And it certainly made you feel better.
0:35:22 > 0:35:24Salicylic acid was effective.
0:35:24 > 0:35:27But it was harsh on the stomach.
0:35:27 > 0:35:31We use it now to burn off warts.
0:35:31 > 0:35:36At Bayer's new drug department, a research chemist, Arthur Eichengrun
0:35:36 > 0:35:38thought he could see a way of changing the molecules,
0:35:38 > 0:35:40to make it more palatable.
0:35:41 > 0:35:44Eichengrun suggested a simple chemical modification,
0:35:44 > 0:35:45which would, in time,
0:35:45 > 0:35:49lead to the production of two incredibly iconic drugs.
0:35:50 > 0:35:53One of them, the world's bestselling painkiller.
0:35:54 > 0:35:57The other, the world's most notorious drug.
0:36:01 > 0:36:03It started innocently enough.
0:36:03 > 0:36:08A young chemist in Eichengrun's team set about modifying salicylic acid,
0:36:08 > 0:36:12using an approach that Eichengrun had suggested.
0:36:12 > 0:36:17The result was crystals of acetylsalicylic acid.
0:36:17 > 0:36:21Just as predicted, it no longer upset the stomach quite so much.
0:36:21 > 0:36:24Eichengrun would eventually name this drug "aspirin".
0:36:26 > 0:36:30Simple chemical modifications could clearly make better drugs.
0:36:30 > 0:36:34Inspired by the this, a chemist in the Bayer team took morphine,
0:36:34 > 0:36:37that powerful painkiller from poppies,
0:36:37 > 0:36:40and tried the same reaction, to see what would happen.
0:36:41 > 0:36:44The result was a chemical called diamorphine.
0:36:44 > 0:36:47Better known to us as "heroin".
0:36:52 > 0:36:54Thank you very much.
0:36:54 > 0:36:58Both of these drugs, aspirin and heroin,
0:36:58 > 0:37:02arrived in front of the chief tester, Heinrich Dreser.
0:37:02 > 0:37:06And he promptly rejected one of them on the grounds it was dangerous.
0:37:06 > 0:37:09Ironically enough, the one he rejected was the aspirin,
0:37:09 > 0:37:12because he said it was bad for the heart.
0:37:12 > 0:37:14But he loved heroin.
0:37:14 > 0:37:18In fact, he named it because of the associations with heroic, powerful.
0:37:18 > 0:37:20And with his ringing endorsement behind it,
0:37:20 > 0:37:24heroin was soon being marketed to the world by Bayer.
0:37:26 > 0:37:29The team at Bayer had accidentally made a far more addictive
0:37:29 > 0:37:31version of morphine.
0:37:31 > 0:37:34And, naturally, it sold fabulously.
0:37:34 > 0:37:38Meanwhile, Eichengrun, irritated that his drug, aspirin,
0:37:38 > 0:37:42was being overlooked, began secretly to carry out tests.
0:37:42 > 0:37:44Eichengrun was convinced the new drug was safe
0:37:44 > 0:37:47so he got a hold of a sample, and he tried it.
0:37:47 > 0:37:49Nothing untoward happened.
0:37:49 > 0:37:52So, next, secretly, he got hold of some Berlin doctors
0:37:52 > 0:37:55and persuaded them to try it on their patients.
0:37:58 > 0:38:01It was given to a small number of doctors and a dentist.
0:38:02 > 0:38:06And a report came back from the dentist.
0:38:06 > 0:38:07He said...
0:38:09 > 0:38:13"I gave it to one of my patients who had a fever.
0:38:14 > 0:38:17"But, to my astonishment, he said his toothache had been
0:38:17 > 0:38:22"eased by taking the acetylsalicylic acid. It relieved pain."
0:38:24 > 0:38:27This was completely unexpected.
0:38:27 > 0:38:30The original salicylic acid brought down fevers,
0:38:30 > 0:38:34but it didn't have any effect on toothache.
0:38:34 > 0:38:38Eichengrun had clearly created something new and powerful.
0:38:40 > 0:38:43So, Eichengrun decided to bypass Dreser
0:38:43 > 0:38:47and went to the Head Of Research at Bayer.
0:38:47 > 0:38:50He authorised more tests and in 1899,
0:38:50 > 0:38:54a year after Bayer had introduced heroin to a grateful nation,
0:38:54 > 0:38:56they started marketing this new drug.
0:38:58 > 0:39:02Aspirin became one of the world's most successful drugs.
0:39:02 > 0:39:0640 billion tablets are eaten every year.
0:39:06 > 0:39:08And it was all thanks to chemists
0:39:08 > 0:39:12tinkering with an industrial waste product - coal tar.
0:39:13 > 0:39:17There was an early illustration of how a simple chemical
0:39:17 > 0:39:19modification to an existing molecule,
0:39:19 > 0:39:23could make a far superior drug, which had additional properties.
0:39:23 > 0:39:27The additional properties of aspirin are due entirely to the acetyl group.
0:39:27 > 0:39:30Without the acetyl group it wouldn't work.
0:39:30 > 0:39:33And, rather amusingly, I keep reading reports of how,
0:39:33 > 0:39:39in ancient times, plants containing salicylates were used as painkillers.
0:39:39 > 0:39:41It's nonsense.
0:39:41 > 0:39:44They might have been used as painkillers - they didn't work.
0:39:44 > 0:39:47The acetyl group of aspirin, which was a synthetic drug,
0:39:47 > 0:39:50had to be present in order to kill pain.
0:39:52 > 0:39:56Despite its universal appeal, it took people more than 70 years
0:39:56 > 0:39:59to understand how aspirin actually works.
0:39:59 > 0:40:03Turns out, nothing like the opiates such as morphine.
0:40:03 > 0:40:05Aspirin acts locally
0:40:05 > 0:40:09and blocks pain long before it gets to the spinal column.
0:40:09 > 0:40:13I'm going to demonstrate using my least favourite plant -
0:40:13 > 0:40:15stinging nettles.
0:40:15 > 0:40:17Ah!
0:40:17 > 0:40:18Ah, yeah!
0:40:18 > 0:40:20That hurts.
0:40:23 > 0:40:27Damaged or irritated tissue releases a lot of chemicals which can
0:40:27 > 0:40:32help healing but which also tend to simulate the pain nerves.
0:40:32 > 0:40:36You could see the results as great swollen marks, inflammation.
0:40:36 > 0:40:40And the same process is often the cause of headache and muscle ache.
0:40:43 > 0:40:45Aspirin and the other anti-inflammatories
0:40:45 > 0:40:47all work in the same way,
0:40:47 > 0:40:49and they block a range of pains.
0:40:49 > 0:40:54Anti-inflammatories stop your body producing the chemicals
0:40:54 > 0:40:57it normally does when tissue has been damaged.
0:40:57 > 0:40:59This not only prevents swelling
0:40:59 > 0:41:02but also the release of chemicals that set off the pain nerves.
0:41:05 > 0:41:07As well as blocking pain,
0:41:07 > 0:41:11aspirin also blocks the hormones that led to platelet production.
0:41:11 > 0:41:13Which means that middle-aged men like me
0:41:13 > 0:41:17take small amounts of it to reduce our risk of getting heart attack.
0:41:17 > 0:41:20Which is pretty ironic when you consider that aspirin
0:41:20 > 0:41:25was originally rejected on the grounds it is bad for the heart.
0:41:25 > 0:41:28Chemists had found ways to ensure that we were no longer
0:41:28 > 0:41:31reliant on plants for our medicines.
0:41:31 > 0:41:34Modifying simple molecules extracted from coal tar had given us
0:41:34 > 0:41:38more powerful drugs than the natural world could provide.
0:41:41 > 0:41:44With misplaced confidence, chemists now decided
0:41:44 > 0:41:47they were going to try and design drugs from scratch.
0:41:47 > 0:41:50The hope was they could produce something lucrative,
0:41:50 > 0:41:52with few side-effects.
0:41:52 > 0:41:57The reality was, they now unleashed onto a wholly unsuspecting world
0:41:57 > 0:42:02a whole new Pandora's box of powerful potions.
0:42:05 > 0:42:09This new phase, trying to make entirely synthetic drugs,
0:42:09 > 0:42:13started as an attempt to correct the limitations of surgical aesthesia.
0:42:16 > 0:42:20Ether was an irritant and made people sick.
0:42:20 > 0:42:22chloroform, discovered soon after,
0:42:22 > 0:42:24caused unacceptably high death rates.
0:42:26 > 0:42:30Perhaps what was needed was a different way of delivering
0:42:30 > 0:42:32antiseptic chemicals into the body.
0:42:34 > 0:42:38The hypodermic needle had been invented in the 1840s.
0:42:38 > 0:42:41And injecting anaesthetic via veins seemed promising.
0:42:43 > 0:42:45When you breathe in a drug,
0:42:45 > 0:42:49what you're trying to do is get a level of the drug into the brain.
0:42:49 > 0:42:55And so if you put it in intravenously it goes to the brain faster.
0:42:55 > 0:42:59So, in 1869, German chemist Oscar Liebreich
0:42:59 > 0:43:03naively started to experiment with a substance called chloral hydrate,
0:43:03 > 0:43:07which had been created many years before.
0:43:07 > 0:43:09The chemical was known to produce chloroform
0:43:09 > 0:43:11when you added an alkali to it.
0:43:12 > 0:43:14So Liebreich thought to himself,
0:43:14 > 0:43:17"If I inject this into the blood, which is mildly alkali,
0:43:17 > 0:43:21"then perhaps I will produce chloroform inside the body."
0:43:21 > 0:43:22So, it's worth doing.
0:43:22 > 0:43:26It's certainly a bold thing to do because instead of trial and error
0:43:26 > 0:43:29he was relying on chemical theory.
0:43:29 > 0:43:32Well, it all seemed to go splendidly at first.
0:43:32 > 0:43:35He injected it into patients and they did indeed...fall asleep.
0:43:37 > 0:43:40His reasoning was flawless, but also completely wrong.
0:43:42 > 0:43:46Chloral hydrate did not produce chloroform when injected into blood,
0:43:46 > 0:43:47but a form of alcohol,
0:43:47 > 0:43:51which did not numb the feeling or pain.
0:43:51 > 0:43:54What Liebreich had stumbled upon was not a painkiller
0:43:54 > 0:43:56but a drug that put people to sleep.
0:43:57 > 0:44:00Chloral hydrate was used in some operations.
0:44:00 > 0:44:03And if a few patients woke up screaming in the middle of it,
0:44:03 > 0:44:06well, they had no memory of doing so afterwards.
0:44:07 > 0:44:10A way of people to sleep safely and quickly
0:44:10 > 0:44:12would be a real boon for surgery.
0:44:12 > 0:44:14But chloral hydrate had its drawbacks.
0:44:16 > 0:44:18It upset the veins, it caused inflammitis -
0:44:18 > 0:44:20irritation in the veins.
0:44:20 > 0:44:25And the duration of action was very long, so patients were very,
0:44:25 > 0:44:27very sleepy for a long time.
0:44:27 > 0:44:32They didn't wake up clear headed and bounce back to work or anything.
0:44:33 > 0:44:37But for those who wanted a long sleep it was great.
0:44:37 > 0:44:40Chemists produced a form that could be taken as a pill,
0:44:40 > 0:44:43the world's first sleeping tablet.
0:44:43 > 0:44:47And within ten years, Britons were taking a tonne of it every day.
0:44:52 > 0:44:54Chloral hydrate soon entered popular culture.
0:44:54 > 0:44:59In 1903, a Chicago newspaper reported that a saloon manager
0:44:59 > 0:45:02had persuaded his employees to put chloral hydrate
0:45:02 > 0:45:06into the drinks of customers suspected of having money.
0:45:07 > 0:45:10And then afterwards they would rob them.
0:45:10 > 0:45:14His name, Mickey Finn, became slang for any spiked drink.
0:45:14 > 0:45:17Now, the importance of chloral hydrate was not just it was
0:45:17 > 0:45:20incredibly popular, but was really one of the first drugs
0:45:20 > 0:45:24to have been designed from scratch with a specific purpose.
0:45:24 > 0:45:28The floodgates were open for any imaginative chemist to make
0:45:28 > 0:45:30a lot of money.
0:45:31 > 0:45:34It was a huge incentive and with their increasing knowledge
0:45:34 > 0:45:38of which molecules had this sedative effect,
0:45:38 > 0:45:41they turned out hundreds of new compounds.
0:45:43 > 0:45:45One of them was to prove a worthy,
0:45:45 > 0:45:48albeit infamous successor to chloral hydrate.
0:45:49 > 0:45:51Because of its use by criminals,
0:45:51 > 0:45:55chloral hydrate gained a somewhat notorious reputation.
0:45:55 > 0:46:00But it would in turn spawn a more notorious anaesthetic.
0:46:00 > 0:46:02Sodium thiopental.
0:46:02 > 0:46:04Otherwise known as the "truth drug".
0:46:08 > 0:46:09And I'm about to try it.
0:46:15 > 0:46:19Sodium thiopental is part of a group of drugs called the "barbiturates",
0:46:19 > 0:46:23and barbiturates were particular popular in the 1950s
0:46:23 > 0:46:26and '60s as a form of sleeping pill.
0:46:26 > 0:46:28They were also very dangerous.
0:46:28 > 0:46:32Famously, Marilyn Monroe died from a barbiturate overdose.
0:46:32 > 0:46:36Sodium thiopental was much faster acting than most barbiturates
0:46:36 > 0:46:39and that made it a great anaesthetic.
0:46:39 > 0:46:43But, oddly enough, it doesn't actually affect pain.
0:46:44 > 0:46:47What Barbiturates do is slow down all the messages
0:46:47 > 0:46:52being sent between nerves in the brain and the spinal column.
0:46:52 > 0:46:54The more barbiturate there is,
0:46:54 > 0:46:57the harder it is for chemical messages to cross the gaps
0:46:57 > 0:47:00between one neuron and the next.
0:47:00 > 0:47:03So, essential, your whole thinking process slows down
0:47:03 > 0:47:06until you fall asleep.
0:47:06 > 0:47:09With thiopental, that happened very quickly indeed.
0:47:09 > 0:47:13And that was just what the anaesthetist in the 1930s wanted.
0:47:14 > 0:47:20Thiopental was developed specifically for getting people to sleep quickly.
0:47:20 > 0:47:23They knew how to keep people asleep once they got them there
0:47:23 > 0:47:25with drugs like ether and chloroform,
0:47:25 > 0:47:28which was still used widely.
0:47:28 > 0:47:33As thiopental starts to act it affects your brain bit by bit.
0:47:33 > 0:47:35And this is the key to one of its more controversial uses.
0:47:39 > 0:47:43The Americans noticed that when patients were in that twilight zone
0:47:43 > 0:47:46halfway between consciousness and unconsciousness,
0:47:46 > 0:47:49they became more chatty, disinhibited
0:47:49 > 0:47:52and also forgot what they'd been talking about afterwards.
0:47:52 > 0:47:55They decided this might form the basis for a truth drug,
0:47:55 > 0:47:57an interrogation drug.
0:47:57 > 0:48:01Now, I'm going to have a go at trying to maintain the fiction
0:48:01 > 0:48:04that I am Dr Michael Mosley, the famous heart surgeon.
0:48:10 > 0:48:13OK, so I'm actually feeling quite anxious at the moment.
0:48:13 > 0:48:17Sodium thiopental has a reputation, not just as a truth drug but also
0:48:17 > 0:48:21because it's used in lethal injections.
0:48:21 > 0:48:23Anaesthetist Austin Leach
0:48:23 > 0:48:25will be monitoring my vital signs throughout.
0:48:25 > 0:48:29These will indicate if my body is feeling pain.
0:48:29 > 0:48:32Before I take the drug, he wants to see how my heart responds
0:48:32 > 0:48:36when he crunches his knuckles against my chest.
0:48:36 > 0:48:38That's quite uncomfortable, yeah.
0:48:41 > 0:48:42Oh...
0:48:43 > 0:48:47My heart rate jumped from 54 to 64 in response to pain.
0:48:49 > 0:48:52Now, it's time to experience the effects of a light dose
0:48:52 > 0:48:53of sodium thiopental.
0:48:57 > 0:49:00I'll just give you a small dose but quite rapidly.
0:49:01 > 0:49:03It's in now.
0:49:08 > 0:49:10Doesn't feel like anything.
0:49:10 > 0:49:11It hasn't got there yet.
0:49:11 > 0:49:13That's probably why I'm not feeling...
0:49:13 > 0:49:16Am I feeling just a bit...? Oh, yes, there it goes.
0:49:18 > 0:49:20Yup, there it is. Blimey! Wow!
0:49:22 > 0:49:24Oh, jeez! Yeah.
0:49:26 > 0:49:29That is like... Oh, that's like drinking a bottle of champagne.
0:49:29 > 0:49:32'So, under the influence of thiopental,
0:49:32 > 0:49:34'can I still lie about my job?'
0:49:34 > 0:49:37I am a cardiac...
0:49:37 > 0:49:39HE LAUGHS
0:49:39 > 0:49:41I'm a cardiac surgeon.
0:49:41 > 0:49:43I'm a world famous cardiac surgeon.
0:49:43 > 0:49:47Would you like to tell me what the last operation you carried out was?
0:49:47 > 0:49:50It was a bypass. They survived.
0:49:51 > 0:49:55But...uh, yeah. I was awesome.
0:49:57 > 0:50:00Now, I'm just going to repeat the pain test...
0:50:00 > 0:50:02- Yeah, OK.- ..in your sternum.
0:50:02 > 0:50:06And tell me how uncomfortable this is.
0:50:06 > 0:50:09Uh, that hurts, but it doesn't really hurt.
0:50:09 > 0:50:12I'm kind of aware of it but I don't care.
0:50:12 > 0:50:14It's actually quite painful.
0:50:14 > 0:50:17'My heart rate jumps right up.
0:50:17 > 0:50:21'My body is still responding to pain but, bizarrely, my brain isn't.
0:50:21 > 0:50:22'It's all very odd.'
0:50:22 > 0:50:27That is so strange.
0:50:27 > 0:50:30'I had just about managed to lie about my job,
0:50:30 > 0:50:32'however unconvincingly.
0:50:32 > 0:50:35'But what would happen if he upped the dose?'
0:50:35 > 0:50:37Oh, yes.
0:50:37 > 0:50:39'The drugs effects aren't predictable,
0:50:39 > 0:50:42'so I don't know what will happen.'
0:50:42 > 0:50:45- Ask me any questions. - So, what is your name?
0:50:45 > 0:50:48- My name is Michael Mosley. - And what is your profession?
0:50:48 > 0:50:50I'm a television producer.
0:50:50 > 0:50:53Well, executive producer. Well, presenter.
0:50:53 > 0:50:56It's a mix of the three of them.
0:50:56 > 0:50:59So, you don't have any history of performing cardiac surgery?
0:50:59 > 0:51:01None whatsoever.
0:51:01 > 0:51:02None whatsoever.
0:51:06 > 0:51:09I am without...
0:51:09 > 0:51:11doubt...
0:51:11 > 0:51:15a good television presenter and not a lousy cardiac surgeon.
0:51:15 > 0:51:17'Part of the reason I caved in so quickly
0:51:17 > 0:51:21'is I had this overwhelming urge to tell the truth.'
0:51:21 > 0:51:24'It's an odd feeling. Quite cathartic.'
0:51:24 > 0:51:27The weird thing is I don't want to lie. I'm feeling so...
0:51:27 > 0:51:30It's not just that I can't.
0:51:30 > 0:51:34It's just I feel so benign towards the world, I don't want to do it.
0:51:34 > 0:51:37I don't want to say I'm Michael Mosley,
0:51:37 > 0:51:39a cardiac surgeon cos I'm not. So...
0:51:42 > 0:51:45'What else I admitted to under the drug's influence must
0:51:45 > 0:51:48'remain for ever secret, from me as well.
0:51:48 > 0:51:50'Afterwards I realised I had forgotten everything
0:51:50 > 0:51:52'that had happened.'
0:51:52 > 0:51:55Did I confess to the fact I'm not a cardiac surgeon?
0:51:55 > 0:51:56So, you can't remember?
0:51:56 > 0:52:00You can't remember what it was you said about your professional status?
0:52:00 > 0:52:04No. I don't know what I was talking about.
0:52:04 > 0:52:05Yeah.
0:52:05 > 0:52:07I feel quite...
0:52:07 > 0:52:08snoozy.
0:52:08 > 0:52:11I feel like I could probably go to sleep now.
0:52:13 > 0:52:15And that's the reason thiopental
0:52:15 > 0:52:18became such a popular anaesthetic drug.
0:52:18 > 0:52:21It puts you to sleep quickly and with just a simple injection.
0:52:24 > 0:52:28A typical anaesthetic of the 1940s would be getting people off
0:52:28 > 0:52:30to sleep with an injection of thiopental.
0:52:30 > 0:52:32And then keeping them asleep with some ether.
0:52:34 > 0:52:37It was a triumph for the chemists.
0:52:37 > 0:52:40A drug that did exactly what it was designed to do.
0:52:40 > 0:52:44But it was only designed to make people unconscious during surgery,
0:52:44 > 0:52:46not to stop them feeling pain.
0:52:48 > 0:52:52What we're aiming to do is to induce unconsciousness,
0:52:52 > 0:52:54so that the patient has no awareness of what would otherwise be
0:52:54 > 0:52:58an extremely unpleasant experience for them.
0:52:58 > 0:53:00To deal with the other aspects, such as pain,
0:53:00 > 0:53:03we need to give supplementary drugs, which are specific painkillers.
0:53:09 > 0:53:12So, chemists nowadays are concentrating their attentions
0:53:12 > 0:53:15not on new anaesthetic drugs, but new painkillers.
0:53:17 > 0:53:21Because we can build pretty well any molecule of any shape
0:53:21 > 0:53:24we want now, by design,
0:53:24 > 0:53:26that's the way in which pharmaceutical companies
0:53:26 > 0:53:29are increasingly orientated.
0:53:29 > 0:53:33It sounds simple. It's actually very, very hard.
0:53:35 > 0:53:38The way chemists create new drugs is essentially the same way
0:53:38 > 0:53:43they did 100 years ago, when they started experimenting with coal tar.
0:53:43 > 0:53:47They take simple molecules and build them up into complex ones.
0:53:49 > 0:53:51These days you'll not be astonished to hear
0:53:51 > 0:53:54things are much more hi-tech.
0:53:54 > 0:53:58Most new drugs start out in a so-called compound library,
0:53:58 > 0:53:59like this one.
0:53:59 > 0:54:03There are over three million different molecules here.
0:54:07 > 0:54:10With this vast repository of molecules to start from,
0:54:10 > 0:54:13chemists can put together almost any compound.
0:54:13 > 0:54:16But there is still the problem of knowing which compounds
0:54:16 > 0:54:17will be useful.
0:54:19 > 0:54:22And in the search for the perfect painkiller,
0:54:22 > 0:54:26a clue to that has come from a most unusual place,
0:54:26 > 0:54:31a few very rare people born without the ability to feel pain.
0:54:32 > 0:54:36In the past, they might have ended up in freak shows.
0:54:36 > 0:54:39But today, some doctors see them as the key to finding a new
0:54:39 > 0:54:41class of painkilling drugs.
0:54:43 > 0:54:46We knew long before we even started thinking about drug development
0:54:46 > 0:54:51that whatever we found in these patients would be a great target for
0:54:51 > 0:54:56a drug because this would reproduce the pain-free existence they have.
0:54:56 > 0:54:59Researchers started by exploring just what people with this
0:54:59 > 0:55:01condition can or cannot feel.
0:55:03 > 0:55:06They could feel when you touch them, they could feel cold.
0:55:06 > 0:55:09So, it so it also told you from this
0:55:09 > 0:55:12that the sensation of pain was different to touch,
0:55:12 > 0:55:16temperature, vibration - you put a vibration on them, they felt it.
0:55:17 > 0:55:21This was encouraging because it suggested
0:55:21 > 0:55:24that pain could be switched off without affecting other nerves.
0:55:24 > 0:55:26The question was, how?
0:55:26 > 0:55:30It turns out these people have inherited a faulty gene,
0:55:30 > 0:55:34which means that their nerves cannot transmit pain signals.
0:55:36 > 0:55:38While all their other nerves are normal,
0:55:38 > 0:55:41their pain nerves are unable to send electrical messages.
0:55:43 > 0:55:47Identifying the problem gene pointed to a particular protein.
0:55:47 > 0:55:50A protein that is necessary for us to feel pain.
0:55:53 > 0:55:56Once they'd found the protein, the next thing that had to do
0:55:56 > 0:56:01was see if they could block its action in normal people,
0:56:01 > 0:56:04see if you could temporarily switch pain off.
0:56:04 > 0:56:08So, you can imagine the idea that what we really know about
0:56:08 > 0:56:11is the shape of the lock.
0:56:11 > 0:56:16And what you're trying to do is to design a molecular key
0:56:16 > 0:56:17which will slot in.
0:56:17 > 0:56:20The problem with building a molecular key is you may not
0:56:20 > 0:56:22be selective enough.
0:56:22 > 0:56:23It's no good switching off pain
0:56:23 > 0:56:28if you also switch off other essential protein production.
0:56:28 > 0:56:31You want to make sure that it is very selective,
0:56:31 > 0:56:34that it doesn't have major effect on other enzymes
0:56:34 > 0:56:36in other crucial pathways in the body.
0:56:36 > 0:56:38Now, you have a real lead.
0:56:38 > 0:56:41Then you have to show that this is really nontoxic.
0:56:42 > 0:56:46Drugs that appear to block just that crucial protein
0:56:46 > 0:56:49are now undergoing a long process of testing.
0:56:49 > 0:56:52And so far they are showing great promise.
0:56:53 > 0:56:59The hope is that they will usher in a new era of pain relief.
0:56:59 > 0:57:03Now you can see that there is an opportunity to think about
0:57:03 > 0:57:09a new approach to treatment of pain that offers hope for millions.
0:57:15 > 0:57:20The journey from herbal medicines to synthetic drugs designed
0:57:20 > 0:57:24and made from scratch has taken a mere 200 years.
0:57:26 > 0:57:29It has been driven by obsession, need,
0:57:29 > 0:57:34happy and sometimes less happy accident.
0:57:35 > 0:57:38And yet, some things have not changed.
0:57:38 > 0:57:40Over the last couple of centuries,
0:57:40 > 0:57:43we have developed a huge range of painkilling drugs,
0:57:43 > 0:57:46from anaesthetics to aspirin.
0:57:46 > 0:57:49But, if I was in terrible pain,
0:57:49 > 0:57:53then the substance I would still use is this - morphine.
0:57:54 > 0:57:57It's very strange to think that in the 200 years
0:57:57 > 0:58:01since it was first isolated by Friedrich Serturner,
0:58:01 > 0:58:06we have developed nothing which is as effective for treating
0:58:06 > 0:58:10excruciating pain as this extraordinary substance.
0:58:20 > 0:58:25Painkillers, wonderful though they are, are only treating symptoms.
0:58:25 > 0:58:29In the next programme, I'll be looking at the remarkable stories
0:58:29 > 0:58:31of those who develop drugs that cure.
0:58:31 > 0:58:34Including the successful attempts to capture and contain
0:58:34 > 0:58:37the greatest mass murderer in history.
0:58:38 > 0:58:42If you'd like to take part in the Open University's quiz on pain,
0:58:42 > 0:58:46or perhaps find out something more about pus and poison,
0:58:46 > 0:58:49then go to the website below and follow the links
0:58:49 > 0:58:51to the Open University.
0:58:54 > 0:58:57Subtitles By Red Bee Media Ltd