0:00:07 > 0:00:12This is Walton Hall in Yorkshire.
0:00:12 > 0:00:17In 1835, it was home to a wealthy and somewhat eccentric gentleman.
0:00:20 > 0:00:24They said he could be seen regularly walking the grounds bare-footed,
0:00:24 > 0:00:27and in the company of an ageing donkey.
0:00:27 > 0:00:29Now they must have been a pretty shabby pair
0:00:29 > 0:00:32but, between them, they took part in one of the more extraordinary
0:00:32 > 0:00:34experiments of the 19th century.
0:00:34 > 0:00:39An experiment that would lead to significant breakthroughs
0:00:39 > 0:00:40in medicine and in surgery,
0:00:40 > 0:00:45and would transform our understanding of poisons.
0:00:45 > 0:00:46Come on then.
0:00:52 > 0:00:56Pain, Pus And Poison has charted the many colourful characters
0:00:56 > 0:01:00who, over the past 200 years, created the medicines
0:01:00 > 0:01:05which protect us from pain, infectious disease and even death.
0:01:08 > 0:01:09Through their heroic efforts,
0:01:09 > 0:01:13chemicals almost magical in their effects were discovered,
0:01:13 > 0:01:17scrutinised, and finally exploited.
0:01:17 > 0:01:22In this programme, I'll reveal the remarkable science behind perhaps
0:01:22 > 0:01:25the most unexpected source of many modern medicines.
0:01:25 > 0:01:27Poisons.
0:01:27 > 0:01:31Poisons that include the planet's most deadly substances.
0:01:32 > 0:01:35A couple of kilos would kill every human on the planet.
0:01:37 > 0:01:40From the natural world to the man-made,
0:01:40 > 0:01:46it's a tale of greed, tragedy, hope and chance.
0:01:48 > 0:01:53What started out as a science expedition looking at bugs
0:01:53 > 0:01:55turns into a cancer therapy.
0:01:55 > 0:01:58To me, I think that's one of the wonders of science.
0:01:58 > 0:02:04So just how far can we go into unlocking the benefits of poisons?
0:02:05 > 0:02:10All medicines are poisons and all poisons should be considered
0:02:10 > 0:02:12as potential medicines.
0:02:12 > 0:02:15This is the story of how we have turned killers
0:02:15 > 0:02:17into cures.
0:02:38 > 0:02:42Poisons have, throughout history, been used to take life,
0:02:42 > 0:02:45whether by suicide, assassination or murder.
0:02:48 > 0:02:50And yet, until the 19th century,
0:02:50 > 0:02:54surprisingly little was known about how they actually work.
0:02:57 > 0:03:00Someone who helped change that was Charles Waterton,
0:03:00 > 0:03:04the colourful squire of Walton Hall.
0:03:04 > 0:03:07He was considered very eccentric.
0:03:07 > 0:03:09He used to sometimes hide under tables
0:03:09 > 0:03:12and bite people's legs at the dinner table.
0:03:12 > 0:03:13He was double-jointed.
0:03:13 > 0:03:17He could scratch behind his ear with his big toe.
0:03:17 > 0:03:19He was an avid tree-climber.
0:03:19 > 0:03:22He climbed trees into his 80s. That's quite strange.
0:03:24 > 0:03:26As well as being an eccentric,
0:03:26 > 0:03:29Waterton was also a man with a passion for knowledge.
0:03:29 > 0:03:32He travelled the globe, collecting the exotic and
0:03:32 > 0:03:37the unusual, not always simply for scientific study.
0:03:37 > 0:03:42He created a taxidermy piece after a customs officer had upset him by
0:03:42 > 0:03:46charging extra duty on the specimens he'd brought back from Guyana.
0:03:46 > 0:03:51He changed the rear end, the arse of a Howler Monkey,
0:03:51 > 0:03:54to look like this customs officer's face,
0:03:54 > 0:03:56which is possibly the perfect insult.
0:04:01 > 0:04:06Waterton spent nearly 20 years living in the Amazonian rainforest,
0:04:06 > 0:04:09where he befriended one of the Amerindian tribes,
0:04:09 > 0:04:10called the Macushi.
0:04:12 > 0:04:15Now what Waterton was really interested in
0:04:15 > 0:04:17was a closely guarded secret -
0:04:17 > 0:04:20a poison that could kill almost any animal,
0:04:20 > 0:04:23and which occasionally they used to kill each other.
0:04:23 > 0:04:27He managed to get the recipe from the Indians.
0:04:27 > 0:04:30It's got some really interesting ingredients.
0:04:30 > 0:04:32We've got the fangs of the Labari Snake,
0:04:32 > 0:04:36and there's also apparently some Black Ants you pound in,
0:04:36 > 0:04:39which are so venomous their sting alone produces a fever.
0:04:39 > 0:04:41But it's actually not those things.
0:04:41 > 0:04:44The key ingredient is a vine which grows in these wilds,
0:04:44 > 0:04:46which is called Wourali.
0:04:46 > 0:04:49It is from this that the poison takes its name,
0:04:49 > 0:04:52and this is the principal ingredient.
0:04:53 > 0:04:57This vine was later identified as strychnos toxifera.
0:04:57 > 0:05:01And the poison from it is known today as Curare.
0:05:04 > 0:05:07Now, these are real samples that Waterton brought back
0:05:07 > 0:05:08200 years ago -
0:05:08 > 0:05:11a bowl in which you'd sort of mix up the ingredients,
0:05:11 > 0:05:13and these are the poison darts.
0:05:13 > 0:05:16In fact, the poison is the black stuff on the end.
0:05:16 > 0:05:19That is Curare. And although it is 200 years old,
0:05:19 > 0:05:23it's still active so I'm not going to touch it.
0:05:23 > 0:05:26Now, Waterton himself brought it back because Europeans
0:05:26 > 0:05:29were absolutely fascinated by Curare and no-one else had
0:05:29 > 0:05:32succeeded in getting the really good stuff in quantities.
0:05:32 > 0:05:36Certainly not enough to do proper experiments with.
0:05:36 > 0:05:40Back home, Waterton was approached by leading vet
0:05:40 > 0:05:42Professor William Sewell,
0:05:42 > 0:05:45and eminent surgeon Sir Benjamin Brodie,
0:05:45 > 0:05:51who wanted to find out exactly how Curare killed its victims.
0:05:51 > 0:05:55Brodie had already tested the poison on small animals,
0:05:55 > 0:05:59but now wanted to experiment on something larger.
0:05:59 > 0:06:02So they used a donkey.
0:06:02 > 0:06:08They injected the unfortunate donkey with enough Curare to kill it.
0:06:08 > 0:06:10Then when it collapsed and stopped breathing,
0:06:10 > 0:06:14they quickly performed an emergency tracheotomy.
0:06:15 > 0:06:17What you do is you get a knife
0:06:17 > 0:06:20and you slit your way into the windpipe here,
0:06:20 > 0:06:24and then what they did is they inserted a pair of bellows into
0:06:24 > 0:06:26the windpipe and pumped away.
0:06:26 > 0:06:30And they really had very little idea of what they were doing.
0:06:30 > 0:06:32They didn't know how long they would have to do it for.
0:06:32 > 0:06:35After about two hours,
0:06:35 > 0:06:37the donkey sort of recovered enough
0:06:37 > 0:06:39to look up and sort of stare at them.
0:06:39 > 0:06:43So they stopped, and the donkey then collapsed.
0:06:43 > 0:06:44So back to the bellows again.
0:06:46 > 0:06:49They kept this up in total for about four hours.
0:06:50 > 0:06:54Until finally, as Waterton wrote in his journal,
0:06:54 > 0:06:57the pumping had saved her from her final disillusion.
0:06:59 > 0:07:03She rose, she walked about without obvious agitation or pain.
0:07:03 > 0:07:05Yes.
0:07:07 > 0:07:11Waterton, Sewell, Brodie and, of course, the donkey,
0:07:11 > 0:07:14had demonstrated something remarkable.
0:07:14 > 0:07:17A discovery that would have an unexpected
0:07:17 > 0:07:19and far-reaching impact.
0:07:20 > 0:07:24They had shown that curare acts on specific muscles,
0:07:24 > 0:07:27including those that enable you to move and breathe.
0:07:29 > 0:07:32Whereas other muscles, including, crucially, the heart,
0:07:32 > 0:07:34were completely unaffected.
0:07:35 > 0:07:38As long as you can keep the patient breathing,
0:07:38 > 0:07:41he, she or it, should survive.
0:07:42 > 0:07:46The key aspects of curare is that it's a muscle relaxant.
0:07:46 > 0:07:49All your voluntary muscles will stop working,
0:07:49 > 0:07:51including the respiratory muscles.
0:07:53 > 0:07:56The three scientists had shown it's possible to keep a patient alive
0:07:56 > 0:08:01while their body is rendered immobile, relaxed by curare.
0:08:01 > 0:08:03Now, in the early 1800s,
0:08:03 > 0:08:06this discovery had no obvious application.
0:08:06 > 0:08:11But 100 years later, it would transform surgery.
0:08:11 > 0:08:14In the mid 20th century, one of my favourite self-experimenters,
0:08:14 > 0:08:16Dr Fred Prescott,
0:08:16 > 0:08:20deliberately injected himself with a pure form of curare
0:08:20 > 0:08:22to demonstrate that it is safe to use
0:08:22 > 0:08:25as a form of muscle relaxant in surgery.
0:08:25 > 0:08:29In fact, since the 1950s, most people who've had major surgery
0:08:29 > 0:08:33will have benefited from curare or one of its modern equivalents.
0:08:35 > 0:08:39And the donkey, she was retired to Walton Hall.
0:08:40 > 0:08:43Charles Waterton wrote in his diaries,
0:08:43 > 0:08:46"She shall be sheltered from the wintry storm.
0:08:46 > 0:08:49"And in summer, she shall have the finest pasture.
0:08:49 > 0:08:52"She will end her days in peace."
0:08:52 > 0:08:55In fact, she did live another 25 years.
0:08:55 > 0:08:58And when she finally died in 1839,
0:08:58 > 0:09:01she got her own obituary in the local paper,
0:09:01 > 0:09:05detailing her contribution to medical science.
0:09:20 > 0:09:24In Victorian Britain, life was harsh and often cut short.
0:09:25 > 0:09:28Life insurance suddenly became a boom industry.
0:09:30 > 0:09:34This led to a surge in financially-motivated murders.
0:09:34 > 0:09:35Many by poison.
0:09:38 > 0:09:42These poisonings would, in turn, have unexpected consequences
0:09:42 > 0:09:44for pharmacy and forensic science.
0:09:48 > 0:09:51One of the most high-profile Victorian cases
0:09:51 > 0:09:54was a woman called Mary Ann Cotton.
0:10:04 > 0:10:07She was married four times.
0:10:07 > 0:10:10Three of her husbands, heavily insured, all died.
0:10:11 > 0:10:14The one who survived seems to have done so
0:10:14 > 0:10:17because he refused to take out insurance, so she left him.
0:10:23 > 0:10:25In all, 10 of her children died
0:10:25 > 0:10:29of what appeared to be gastric-related illnesses.
0:10:30 > 0:10:32Tragic and terribly sad,
0:10:32 > 0:10:35but fortunately, most of them were insured.
0:10:37 > 0:10:41Her mother, her sister-in-law and her lover
0:10:41 > 0:10:46also died and in each case, she benefited.
0:10:50 > 0:10:53By 1872, the unfortunate Mary Ann
0:10:53 > 0:10:57had lost an astonishing 16 close friends
0:10:57 > 0:10:59or family members.
0:10:59 > 0:11:00But there was one left.
0:11:00 > 0:11:03Her seven-year-old stepson, Charles Cotton.
0:11:03 > 0:11:06Now, she tried to give him away to the local workhouse,
0:11:06 > 0:11:08but they wouldn't have him without her.
0:11:10 > 0:11:12Young Charles soon died.
0:11:14 > 0:11:16The manager of the workhouse, however, got suspicious
0:11:16 > 0:11:20when he heard about the death of the child and he contacted the police.
0:11:20 > 0:11:24They investigated and exhumed the body of young Charles.
0:11:26 > 0:11:29They suspected foul play.
0:11:29 > 0:11:33And, not surprisingly, wondered if Mary Ann had poisoned him.
0:11:33 > 0:11:35BELLS PEAL
0:11:37 > 0:11:39They thought they knew how she'd done it.
0:11:41 > 0:11:42With arsenic.
0:11:46 > 0:11:48Arsenic was an excellent way to kill somebody.
0:11:48 > 0:11:50It's known as a cumulative poison,
0:11:50 > 0:11:52which means that you don't excrete the dose.
0:11:52 > 0:11:54So in other words, the more you take,
0:11:54 > 0:11:56it builds up more and more in the body.
0:11:56 > 0:11:59And it was very easy to administer in food.
0:11:59 > 0:12:02So it just looked like somebody was dying of natural causes.
0:12:04 > 0:12:07The trial of Mary Ann Cotton would hinge on whether
0:12:07 > 0:12:11they could find traces of arsenic in the body of Charles Cotton.
0:12:11 > 0:12:14Now, forensic science was still in its infancy,
0:12:14 > 0:12:17but they did have a good test for arsenic.
0:12:17 > 0:12:18The reason for that is,
0:12:18 > 0:12:22there was an awful lot of arsenic-poisoning around.
0:12:24 > 0:12:26This test is called the Reinsch test.
0:12:26 > 0:12:28And it was the one used to discover
0:12:28 > 0:12:32whether Mary Ann had poisoned little Charles.
0:12:32 > 0:12:35A sample from the boy's stomach and intestines
0:12:35 > 0:12:37was heated with acid and copper.
0:12:40 > 0:12:43If arsenic was present, the copper would turn dark grey.
0:12:44 > 0:12:47And when placed on paper soaked in mercury bromide,
0:12:47 > 0:12:51produce a tell-tale yellowy-brown stain.
0:12:53 > 0:12:57And when they did this test on the body of poor little Charles,
0:12:57 > 0:13:02they discovered that he had indeed died of a lethal dose of arsenic.
0:13:02 > 0:13:04His stepmother Mary Ann
0:13:04 > 0:13:07was convicted of his murder on the basis of this
0:13:07 > 0:13:11and she was hanged in Durham jail in March, 1873.
0:13:11 > 0:13:15She was never taken to trial for the mysterious deaths
0:13:15 > 0:13:19of her mother, three husbands, two friends
0:13:19 > 0:13:21and 10 other children.
0:13:24 > 0:13:28Throughout the 19th century, tales of sinister poisoners
0:13:28 > 0:13:33and unfortunate accidents filled the newspapers.
0:13:33 > 0:13:37And it was because arsenic was such a silent and prolific killer
0:13:37 > 0:13:41that some of the earliest techniques in forensic science were developed.
0:13:41 > 0:13:44But arsenic was about to do more than that.
0:13:44 > 0:13:46It was about to shape the development
0:13:46 > 0:13:48of the modern drug industry.
0:14:02 > 0:14:04Now, I'm feeling quite nervous
0:14:04 > 0:14:07because this stuff is really, really nasty.
0:14:07 > 0:14:09It actually is a mineral,
0:14:09 > 0:14:13and even a tiny, tiny amount,
0:14:13 > 0:14:16less than a hundredth of an ounce, would kill you.
0:14:16 > 0:14:19As a poison, it is almost unrivalled
0:14:19 > 0:14:22because it's completely tasteless, dissolves in hot water
0:14:22 > 0:14:25and it takes so little to kill.
0:14:25 > 0:14:29I'm going to put that back in there and then...
0:14:31 > 0:14:33Ooo! Go and wash my hands.
0:14:36 > 0:14:39Arsenic trioxide was marketed as a rat poison.
0:14:39 > 0:14:42It was cheap and easily available.
0:14:42 > 0:14:45Children would blithely collect it from the shops,
0:14:45 > 0:14:48along with tea, sugar and dried fruits.
0:14:48 > 0:14:52A fact satirised in this Punch cartoon from 1849.
0:14:55 > 0:14:59And yet there was clear evidence of it being used to murder people.
0:14:59 > 0:15:02So pressure was growing to bring this deadly poison
0:15:02 > 0:15:04under some sort of control.
0:15:05 > 0:15:07The Pharmaceutical Society,
0:15:07 > 0:15:10along with what became the British Medical Association,
0:15:10 > 0:15:14got together in 1849, went to Parliament
0:15:14 > 0:15:17and lobbied for a new law to actually stop these poisonings.
0:15:18 > 0:15:23As consequence, a new act was passed which was the 1851 Arsenic Act,
0:15:23 > 0:15:27which greatly restricted the sales of arsenic.
0:15:27 > 0:15:30The new act said that if you were selling arsenic over the counter,
0:15:30 > 0:15:33then you had to keep a record.
0:15:33 > 0:15:35You also had to know the person you were selling it to.
0:15:35 > 0:15:38And finally, in future, all arsenic
0:15:38 > 0:15:41would have to be coloured with soot or indigo.
0:15:41 > 0:15:44So presumably, if your husband or wife was trying to poison you,
0:15:44 > 0:15:46then you had a better chance of detecting it.
0:15:46 > 0:15:49It had even been proposed
0:15:49 > 0:15:52that women should be banned from buying arsenic.
0:15:52 > 0:15:54But that measure didn't make it onto the statute book.
0:15:57 > 0:16:00Although the act restricted who could buy arsenic,
0:16:00 > 0:16:02it made no mention of who could sell it.
0:16:05 > 0:16:07So inevitably, the deaths continued.
0:16:09 > 0:16:12A few years, and many murders later,
0:16:12 > 0:16:15Parliament finally introduced further laws
0:16:15 > 0:16:19to restrict the sale of the more obvious poisons.
0:16:19 > 0:16:24More importantly, they also created the trade of chemists and druggists.
0:16:24 > 0:16:27The Arsenic Act and other acts that followed
0:16:27 > 0:16:31finally brought arsenic and a whole range of other dangerous chemicals
0:16:31 > 0:16:33under some sort of control.
0:16:33 > 0:16:36Now, I do think it is gloriously ironic
0:16:36 > 0:16:40that it was from all these poisonings, accidents and murders
0:16:40 > 0:16:44that the modern, legitimate business of pharmacy emerged.
0:16:50 > 0:16:52At the start of the 19th century,
0:16:52 > 0:16:56poisons had been mysterious and deadly compounds.
0:16:56 > 0:16:59Convenient for killing yourself or others.
0:16:59 > 0:17:02By the middle of the century, a more rational understanding
0:17:02 > 0:17:05of how they worked was emerging.
0:17:05 > 0:17:08And along with a legal and professional framework
0:17:08 > 0:17:10designed to control their use,
0:17:10 > 0:17:14it would lead to a new era of scientific discovery.
0:17:15 > 0:17:18This is belladonna, deadly nightshade.
0:17:18 > 0:17:21And there is certainly enough there to kill me.
0:17:21 > 0:17:26Now, belladonna in Italian means beautiful lady.
0:17:26 > 0:17:28And that's because in the past, elegant ladies
0:17:28 > 0:17:30would get the juice from this plant
0:17:30 > 0:17:33and they would use it to dilate their pupils
0:17:33 > 0:17:36in the hope that it would make them look more attractive.
0:17:36 > 0:17:41In the 19th century, they managed to isolate the active ingredient
0:17:41 > 0:17:43from the belladonna plant.
0:17:43 > 0:17:44It's a substance called atropine.
0:17:44 > 0:17:49And ophthalmologists started to use this to help them examine the eye.
0:17:49 > 0:17:52Now, I have the modern equivalent here.
0:17:52 > 0:17:55And I'm going to put some in my eye to see what happens.
0:18:01 > 0:18:02Ooo! That does sting.
0:18:06 > 0:18:08Over the last few minutes,
0:18:08 > 0:18:11the focus in this eye has gradually gone.
0:18:11 > 0:18:14And I think you can tell that my pupil
0:18:14 > 0:18:17is a great deal bigger in this eye than that eye.
0:18:17 > 0:18:19But am I more attractive?
0:18:22 > 0:18:24One of the reasons why having a big pupil
0:18:24 > 0:18:26is supposed to make you look more attractive
0:18:26 > 0:18:28is because when you look at somebody
0:18:28 > 0:18:32and you find them sexually attractive, then your pupils expand.
0:18:32 > 0:18:35So it's really just me saying to you,
0:18:35 > 0:18:38at this moment, I find you very, very attractive.
0:18:38 > 0:18:41And that's why you find me very, very attractive.
0:18:42 > 0:18:44Atropine is extremely toxic
0:18:44 > 0:18:47and ladies dying to look more beautiful
0:18:47 > 0:18:49were at risk of doing just that.
0:18:49 > 0:18:53And yet, oddly enough, the best treatment for atropine overdose
0:18:53 > 0:18:56turned out to be another poison.
0:19:11 > 0:19:13In 1864 in Prague,
0:19:13 > 0:19:16a doctor was summoned to treat four prisoners
0:19:16 > 0:19:19who had broken into a local dispensary,
0:19:19 > 0:19:21and, thinking they were drinking alcohol,
0:19:21 > 0:19:25had drunk a large quantity of liquid containing atropine.
0:19:25 > 0:19:29When the doctor got there, they had clear signs of atropine poisoning.
0:19:30 > 0:19:34The men were seriously ill, lying prostate on the ground,
0:19:34 > 0:19:39vomiting profusely, with these huge dilated eyes.
0:19:40 > 0:19:43The doctor had no idea how to treat them.
0:19:44 > 0:19:49Then an ophthalmologist friend of his suggested something radical.
0:19:49 > 0:19:50Poison the men even further.
0:19:51 > 0:19:54But this time, with a different poison.
0:19:54 > 0:19:56Extract of Calabar bean.
0:19:58 > 0:20:03Calabar beans contain a number of pharmacologically-active alkaloids,
0:20:03 > 0:20:05one of which is physostigmine,
0:20:05 > 0:20:07which constricts the pupils.
0:20:07 > 0:20:10Unlike atropine, which dilates them.
0:20:10 > 0:20:12The hope was it could also reverse
0:20:12 > 0:20:15the other more serious effects of atropine.
0:20:17 > 0:20:20The doctor felt he had nothing to lose,
0:20:20 > 0:20:22so he took the man who was sickest,
0:20:22 > 0:20:24whose temperature had gone up
0:20:24 > 0:20:27and who really looked as though he was on the brink of death.
0:20:27 > 0:20:30And he got him, not without difficulty,
0:20:30 > 0:20:33to consume some of this second poison.
0:20:33 > 0:20:36Within a few hours, his temperature had come down.
0:20:36 > 0:20:39Within a day, he was completely cured.
0:20:42 > 0:20:45Calabar beans and atropine have opposing actions.
0:20:45 > 0:20:47They can be used to cancel each other out.
0:20:47 > 0:20:49So effectively, one can be used
0:20:49 > 0:20:51as the antidote to the other, either way around.
0:20:54 > 0:20:57And it wasn't long before poisons began to be commonplace
0:20:57 > 0:21:00in a physician's drug cabinet.
0:21:00 > 0:21:02In fact these, days, atropine is often used
0:21:02 > 0:21:05to reverse the effects of insecticide poisoning
0:21:05 > 0:21:08and it's also used to treat some forms of heart disease.
0:21:16 > 0:21:20During the 19th century, researchers looking into poisons
0:21:20 > 0:21:24were, on the whole, trying to find ways to make them more productive,
0:21:24 > 0:21:25more beneficial.
0:21:25 > 0:21:27At the start of the 20th century,
0:21:27 > 0:21:30things took an altogether bleaker, darker turn.
0:21:38 > 0:21:39World War I.
0:21:43 > 0:21:47It would leave 17 million people dead or missing in action.
0:21:50 > 0:21:52It was a living hell.
0:21:53 > 0:21:58And it was made even more hellish by the work of industrial chemists.
0:22:10 > 0:22:14And during 1917, troops based in Ypres, Belgium,
0:22:14 > 0:22:17reported a strange peppery smell in the air
0:22:17 > 0:22:22and a golden, shimmering cloud that surrounded their feet.
0:22:22 > 0:22:27Within 24 hours, they had started to itch uncontrollably.
0:22:27 > 0:22:30And they came up in horrible, painful blisters
0:22:30 > 0:22:34and vile, incurable sores.
0:22:34 > 0:22:38Those who had inhaled too deeply started to cough up blood.
0:22:38 > 0:22:41The troops had been poisoned by mustard gas.
0:22:53 > 0:22:56Gas masks like this one were state of the art at the time,
0:22:56 > 0:22:59but they were pretty useless against mustard gas.
0:22:59 > 0:23:03The problem is, mustard gas can be absorbed through the skin.
0:23:03 > 0:23:07Even if you were fully clothed, you were not fully protected.
0:23:09 > 0:23:11Gasping, spluttering, drowning,
0:23:11 > 0:23:14it could take up to six weeks to die,
0:23:14 > 0:23:16and it was a terrible death.
0:23:16 > 0:23:20Now, mustard gas was not the first of the poison gasses,
0:23:20 > 0:23:23it was actually one of a number that had been weaponised
0:23:23 > 0:23:25by the Kaiser Wilhelm Institute
0:23:25 > 0:23:29under the directorship of a man called Fritz Haber.
0:23:30 > 0:23:34Fritz Haber was a professor at the prestigious University of Karlsruhe.
0:23:34 > 0:23:37And was married to fellow chemist Clara Immerwahr.
0:23:40 > 0:23:44Haber would go on to win a Nobel Prize in chemistry,
0:23:44 > 0:23:48but he also played a major role in the manufacture of chemical weapons.
0:23:49 > 0:23:52He really pressed the Germans, who...
0:23:52 > 0:23:55The German military didn't have much regard for science.
0:23:55 > 0:23:57..pressed the Germans to see what science could do
0:23:57 > 0:24:00in providing them with explosives and chemical weapons,
0:24:00 > 0:24:01and he oversaw the first use
0:24:01 > 0:24:04of chemical warfare on the Western Front.
0:24:07 > 0:24:11He saw it as an efficient way to fight a war.
0:24:11 > 0:24:14And he didn't think it was especially inhumane.
0:24:14 > 0:24:18After all, he said, death is death, however it is inflicted.
0:24:22 > 0:24:27His wife, Clara, pleaded with him to stop working on gas warfare.
0:24:28 > 0:24:32He angrily and publicly denounced her as a traitor.
0:24:39 > 0:24:43Gas warfare was an horrific, but extremely effective new weapon.
0:24:43 > 0:24:46It not only crippled and killed,
0:24:46 > 0:24:49but also instilled terror right across the battlefield.
0:24:52 > 0:24:55Casualties from the first use were estimated at 5,000 to 10,000 dead,
0:24:55 > 0:24:58with many, many more injured.
0:24:58 > 0:25:01And Haber was delighted, as were the German military.
0:25:02 > 0:25:07Haber was promoted to captain and he returned to Berlin in triumph,
0:25:07 > 0:25:10but the couple continued to argue
0:25:10 > 0:25:14because Clara was deeply unhappy with what he was doing.
0:25:14 > 0:25:19Haber, however, felt that he had an absolute scientific
0:25:19 > 0:25:22and patriotic duty to continue working in chemical warfare.
0:25:24 > 0:25:28Finally, and tragically, Clara took matters into her own hands.
0:25:37 > 0:25:39In the middle of the night,
0:25:39 > 0:25:43Clara silently removed her husband's pistol from its holster.
0:25:53 > 0:25:55She stepped outside.
0:25:55 > 0:25:59And then she shot herself through the heart.
0:26:04 > 0:26:07Later that day, Fritz Haber left for the Eastern Front
0:26:07 > 0:26:11to oversee the next gas release against the Russians.
0:26:13 > 0:26:17He left behind his grieving 13-year-old son,
0:26:17 > 0:26:20who had been the one to discover his mother's dead body.
0:26:24 > 0:26:29Haber continued to enthusiastically promote the use of poisoned gas.
0:26:29 > 0:26:33And his colleagues would go on to develop even more deadly nerve gasses.
0:26:34 > 0:26:38One reason why World War I became known as the chemist's war.
0:26:42 > 0:26:45But the story of mustard gas does not end here.
0:26:50 > 0:26:5320 years later, with World War II looming,
0:26:53 > 0:26:56researchers at Yale University's School of Medicine
0:26:56 > 0:27:00retreated to their labs to try and create antidotes to mustard gas.
0:27:05 > 0:27:07They feared a repeat of World War I.
0:27:09 > 0:27:11But what they discovered would lead them
0:27:11 > 0:27:13into a very different kind of battle.
0:27:14 > 0:27:18Two of the doctors involved were Louis Goodman and Alfred Gilman.
0:27:23 > 0:27:27Working these libraries, they delved into the medical records
0:27:27 > 0:27:31of soldiers who had been exposed to mustard gas in the First World War.
0:27:31 > 0:27:35And what they found, amongst other things, was that these soldiers
0:27:35 > 0:27:39had surprisingly low white blood cell count.
0:27:40 > 0:27:44This chance discovery would lead to a radically new treatment
0:27:44 > 0:27:47for one of our greatest killers. Cancer.
0:27:51 > 0:27:55Cancer occurs as a result of mutations in the cells of DNA.
0:27:55 > 0:28:00These genetic mutations either promote excess cell growth
0:28:00 > 0:28:04or remove the normal safeguards that limit cell division.
0:28:04 > 0:28:07Either way, the cell begins to divide uncontrollably.
0:28:09 > 0:28:12One type of cell that is particularly prone to mutation
0:28:12 > 0:28:15is the leucocyte, or white blood cell.
0:28:17 > 0:28:19Goodman and Gilman thought to themselves,
0:28:19 > 0:28:23if mustard gas can destroy normal white cells,
0:28:23 > 0:28:26perhaps it can also destroy malignant ones.
0:28:26 > 0:28:28It was certainly worth a go.
0:28:31 > 0:28:32After successful animal trials,
0:28:32 > 0:28:35they looked for a human volunteer
0:28:35 > 0:28:38with white blood cell cancer to test their theories on.
0:28:39 > 0:28:42They found a patient with advanced lymphoma,
0:28:42 > 0:28:45known to us only by his initials, JD.
0:28:48 > 0:28:50These are JD's original medical notes,
0:28:50 > 0:28:53which were lost for nearly 70 years.
0:28:53 > 0:28:56And I'm the first person outside the Yale medical community
0:28:56 > 0:28:58to lay my hands on them.
0:28:58 > 0:29:02They tell a fascinating and poignant story.
0:29:04 > 0:29:08JD was a Polish immigrant in his 40s. A metal worker.
0:29:09 > 0:29:13He was riddled with cancer and had a massive tumour on his jaw.
0:29:15 > 0:29:18When he first came in, the tumour had progressed
0:29:18 > 0:29:20to the point where he could not swallow,
0:29:20 > 0:29:22he could not sleep at night,
0:29:22 > 0:29:25he could not fold his arms across his chest
0:29:25 > 0:29:29because the lymph nodes in cancer under his arms were so massive.
0:29:29 > 0:29:34And he was really encased front and back by tumour, and up to his face.
0:29:34 > 0:29:37And he was just absolutely miserable.
0:29:40 > 0:29:42His doctors tried everything they could.
0:29:43 > 0:29:45But the prognosis was not good.
0:29:48 > 0:29:52They had a case conference and concluded it with this line,
0:29:52 > 0:29:56"the patient's outlook is utterly hopeless on the present regiment."
0:29:58 > 0:30:02With nowhere else to turn, JD agreed to try the experimental drug,
0:30:02 > 0:30:04based on deadly mustard gas.
0:30:08 > 0:30:13The notes say that at 10:00am on 27th August, 1942,
0:30:13 > 0:30:15they gave him the first injection
0:30:15 > 0:30:19of what they call synthetic lymphocidal chemical,
0:30:19 > 0:30:22but which was, in fact, nitrogen mustard.
0:30:25 > 0:30:29Because of the war, even JD's treatment was a secret.
0:30:29 > 0:30:32They couldn't name nitrogen mustard.
0:30:32 > 0:30:36In the records, it was simply called, Substance X.
0:30:38 > 0:30:41X given at 4:30pm and then again,
0:30:41 > 0:30:44X given at 9:30am the following morning.
0:30:47 > 0:30:52He received a number of treatments using nitrogen mustard.
0:30:52 > 0:30:54And with each one, he became a little bit better.
0:30:54 > 0:30:56He could actually sleep at night,
0:30:56 > 0:31:00he could swallow, he could eat, he was much more comfortable.
0:31:00 > 0:31:04The pain became minimal
0:31:04 > 0:31:05and he was absolutely thrilled.
0:31:07 > 0:31:09Although not fully understood at the time,
0:31:09 > 0:31:14nitrogen mustard works by binding to the DNA of dividing cells.
0:31:15 > 0:31:19This triggers the cells' self-destruct mechanism.
0:31:19 > 0:31:23Instead of dividing, the cells shut down and break apart.
0:31:23 > 0:31:26And the cancer, hopefully, is destroyed.
0:31:30 > 0:31:34This was the first time that a drug had been used to treat cancer.
0:31:37 > 0:31:38This was monumental.
0:31:38 > 0:31:41I mean, it was a huge moment in the history of medicine.
0:31:41 > 0:31:45It is the beginnings of what we now call chemotherapy.
0:31:45 > 0:31:48And very strange to think that it all started
0:31:48 > 0:31:51in the horrors of the trenches of the First World War.
0:31:54 > 0:31:56All the chemo drugs that followed
0:31:56 > 0:32:00have had the same basic mechanism of action.
0:32:00 > 0:32:02They are poisonous to living cells.
0:32:05 > 0:32:09If you get the dosing right then you can kill the cancer
0:32:09 > 0:32:10without killing the patient,
0:32:10 > 0:32:14and in fact, nitrogen mustard is still used for
0:32:14 > 0:32:16the treatment of some cancers.
0:32:17 > 0:32:20But cancers are persistent.
0:32:20 > 0:32:24Even today the prospect for people with advanced cancers is often poor.
0:32:25 > 0:32:28For JD, treatment came too late.
0:32:32 > 0:32:34To say that he enjoyed a few months
0:32:34 > 0:32:39is probably accurate but ultimately he followed a downhill course.
0:32:41 > 0:32:46JD, the world's first chemotherapy patient, survived for six months.
0:32:48 > 0:32:53There's just one entry for the 1st of December 1942.
0:32:53 > 0:32:56It simply says, "Died."
0:32:58 > 0:33:00JD died peacefully,
0:33:00 > 0:33:04unaware of the impact his life and death would have.
0:33:07 > 0:33:11His story pulls the strings of your heart. It really does.
0:33:12 > 0:33:17I think that he was a sad person,
0:33:17 > 0:33:21with few friends, with a devastating disease
0:33:21 > 0:33:26and he made a huge contribution to management of cancer.
0:33:27 > 0:33:30So we are grateful to him for that,
0:33:30 > 0:33:34and we share his agony at the same time.
0:33:44 > 0:33:46The field of chemotherapy,
0:33:46 > 0:33:50and indeed the very idea of using poisons as medicines,
0:33:50 > 0:33:53poses fundamental questions about toxicity.
0:33:54 > 0:33:58How do you decide which substances are poisonous and which are not?
0:34:00 > 0:34:02After all, even the ancients realised
0:34:02 > 0:34:05that poisonous is a relative term.
0:34:06 > 0:34:11"All substances are poisonous. There is none that is not poisonous."
0:34:11 > 0:34:14Now, that's according to 16th century doctor
0:34:14 > 0:34:17and chemist, Paracelsus.
0:34:17 > 0:34:20He goes on to add, "If it's simply the dose which determines
0:34:20 > 0:34:24"whether a substance is poisonous or not."
0:34:25 > 0:34:29Even water can be lethal if you drink enough of it.
0:34:29 > 0:34:31Too much causes brain cells to swell,
0:34:31 > 0:34:33which can lead to coma and death.
0:34:36 > 0:34:40So how much water would I have to drink for it to kill me?
0:34:40 > 0:34:43About seven litres drunk over a few hours,
0:34:43 > 0:34:45that would leave me with a 50/50 chance of surviving,
0:34:45 > 0:34:51and when it comes to coffee, about 100 would probably finish me off.
0:34:52 > 0:34:55And it's not just the amount that matters,
0:34:55 > 0:34:59the toxicity of a substance can depend on what species you are.
0:35:01 > 0:35:06Now, I absolutely love chocolate. If I were to eat a bar this big
0:35:06 > 0:35:09then it would probably make me feel a little bit queasy
0:35:09 > 0:35:10but nothing worse.
0:35:10 > 0:35:12However, it would be a very different story
0:35:12 > 0:35:14if I was a dog like Dolly here.
0:35:14 > 0:35:17Because chocolate is very bad for dogs.
0:35:17 > 0:35:22Two bars this size on a dog this size, could well be lethal.
0:35:22 > 0:35:26The thing is it contains a substance called theobromine.
0:35:26 > 0:35:30And theobromine in dogs causes vomiting,
0:35:30 > 0:35:32heart problems, and convulsions.
0:35:32 > 0:35:35So this is for me and not for you.
0:35:38 > 0:35:41Toxicity also varies according to the type of exposure.
0:35:41 > 0:35:44Whether the poison just touches the skin or is inhaled,
0:35:44 > 0:35:47ingested or even injected.
0:35:49 > 0:35:53Nonetheless, it is extremely useful to have a comparative scale
0:35:53 > 0:35:55of how toxic various substances are.
0:35:57 > 0:36:00One measurable lethality is the LD50,
0:36:00 > 0:36:02the lethal dose 50%.
0:36:02 > 0:36:05In other words, how much of a substance
0:36:05 > 0:36:07would kill half of these mice?
0:36:07 > 0:36:11Although now rarely tested on rodents,
0:36:11 > 0:36:14the concept of LD50 has stuck.
0:36:14 > 0:36:20To allow for size, doses are given per kilogram of body mass.
0:36:21 > 0:36:24On a standardised LD50 scale,
0:36:24 > 0:36:26water comes in at greater than 90,000 milligrams
0:36:26 > 0:36:29per kilogram of body mass.
0:36:29 > 0:36:33Pure alcohol is fatal to half the population
0:36:33 > 0:36:36at 7,000 milligrams per kilogram.
0:36:36 > 0:36:39While caffeine weighs in at 192.
0:36:40 > 0:36:47Arsenic has an LD50 of 14, curare is lethal at only 0.5.
0:36:49 > 0:36:51So while anything can be poisonous,
0:36:51 > 0:36:55substances with an LD50 less than 100 milligrams per kilogram
0:36:55 > 0:36:58tend to be called poisons.
0:36:59 > 0:37:03On this scale most chemotherapy agents, including nitrogen mustard,
0:37:03 > 0:37:07would register between one and four milligrams per kilogram.
0:37:12 > 0:37:15By the 1950s, researchers had turned some poisons
0:37:15 > 0:37:18into effective drugs.
0:37:18 > 0:37:22Natural plant poisons like curare were being used in surgery,
0:37:23 > 0:37:26and synthetics like nitrogen mustard,
0:37:26 > 0:37:28were having an impact on cancer.
0:37:30 > 0:37:33They were just a small part of a new enthusiasm
0:37:33 > 0:37:36for pharmaceutical products.
0:37:36 > 0:37:40But in this dash for cash, the authorities overlooked the fact
0:37:40 > 0:37:45that while poisons can be medicines, medicines can also be poisons.
0:37:47 > 0:37:52It was only a matter of time before something went badly wrong.
0:38:01 > 0:38:04Amongst those rushing out new drugs, was a German company
0:38:04 > 0:38:06called Chemi Grunenthal.
0:38:08 > 0:38:10Staffed by many former Nazis,
0:38:10 > 0:38:13they were searching for lucrative new medicines
0:38:13 > 0:38:15and had created a chemical
0:38:15 > 0:38:17that looked particularly interesting.
0:38:18 > 0:38:22Structurally, the drug was very similar to barbiturates,
0:38:22 > 0:38:24a class of drug that was then widely being used
0:38:24 > 0:38:27by anyone who had a sleep disorder.
0:38:27 > 0:38:29So the company decided to send it off to doctors
0:38:29 > 0:38:34and get them to try it on their patients who had sleeping problems.
0:38:34 > 0:38:38The new drug did well, and was soon being heavily marketed
0:38:38 > 0:38:43as effective against insomnia, coughs, colds and headaches.
0:38:43 > 0:38:45Oddly enough, it was a sedative
0:38:45 > 0:38:49but it was also known to be quite useful in morning sickness
0:38:49 > 0:38:51for pregnant women.
0:38:51 > 0:38:54It was distributed initially
0:38:54 > 0:38:56under the brand name Distaval.
0:38:59 > 0:39:02By 1960, Distaval was sold throughout Europe,
0:39:02 > 0:39:05South America, Africa, Canada and Australia.
0:39:10 > 0:39:13Around this time the number of babies being born
0:39:13 > 0:39:16with deformed or missing limbs and organs,
0:39:16 > 0:39:18well, they started to rise.
0:39:18 > 0:39:21Initially just a few, but then the numbers took off.
0:39:21 > 0:39:24Now this was clearly really distressing,
0:39:24 > 0:39:27and something was going on. The problem was, the doctors
0:39:27 > 0:39:30didn't have a clue what.
0:39:31 > 0:39:36Several traumatic years passed before the cause was finally found,
0:39:36 > 0:39:37when a young Australian doctor
0:39:37 > 0:39:40looked at the mothers rather than the babies.
0:39:41 > 0:39:45The only thing he could find was that these women had all suffered
0:39:45 > 0:39:48from morning sickness in their early months of their pregnancy.
0:39:48 > 0:39:52And they had all been prescribed the drug Distaval,
0:39:52 > 0:39:56which is now more commonly known by its generic name,
0:39:56 > 0:39:58Thalidomide.
0:39:59 > 0:40:03It has been estimated that around 10,000 babies
0:40:03 > 0:40:06were severely disabled by Thalidomide.
0:40:06 > 0:40:09Half of whom failed to live to adulthood.
0:40:14 > 0:40:18The situation in America, however, was very different.
0:40:20 > 0:40:24It was 1960, the year before the link between Thalidomide
0:40:24 > 0:40:27and birth defects would be made.
0:40:27 > 0:40:30Frances Kelsey was just starting out her new job
0:40:30 > 0:40:33as the Food And Drug Administration.
0:40:33 > 0:40:36Her first assignment was to review an application
0:40:36 > 0:40:39to market Thalidomide.
0:40:40 > 0:40:43Since it was already on sale in the rest of the world,
0:40:43 > 0:40:47and since no-one yet knew that it caused birth defects,
0:40:47 > 0:40:50it should have been a case of simply approving it.
0:40:51 > 0:40:55But Kelsey strongly felt the application was not up to standard.
0:40:57 > 0:41:00Here's a person who was very well trained in pharmacology,
0:41:00 > 0:41:03and medical practice.
0:41:03 > 0:41:08And so when she saw the application she was kind of appalled.
0:41:08 > 0:41:14It struck her more as testimonials than good solid clinical research.
0:41:14 > 0:41:17And she sent a letter responding to the application
0:41:17 > 0:41:22saying that in its present form it could not be accepted
0:41:22 > 0:41:25and to submit additional data.
0:41:27 > 0:41:31Another application was submitted to the FDA
0:41:31 > 0:41:35But Kelsey was still not convinced by the safety data.
0:41:35 > 0:41:38So despite mounting pressure from the manufacturer,
0:41:38 > 0:41:43she again refused Thalidomide a licence.
0:41:45 > 0:41:50There was a back and forth between FDA and the mail company.
0:41:52 > 0:41:55The mail company was getting quite annoyed, honestly,
0:41:55 > 0:41:58threatening to go not only to the supervisor,
0:41:58 > 0:42:02the head of the Bureau of Medicine, but the Commissioner of FDA.
0:42:02 > 0:42:04But she stood her ground.
0:42:04 > 0:42:07She stood her ground as a scientist,
0:42:07 > 0:42:09she stood her ground as an FDA official
0:42:09 > 0:42:12who of course had to uphold the law,
0:42:12 > 0:42:15and the law required that the drug had to be safe.
0:42:15 > 0:42:18She persevered through this whole process.
0:42:20 > 0:42:25Kelsey continually refused to allow Thalidomide a licence.
0:42:25 > 0:42:28When in 1961 the facts finally came out,
0:42:28 > 0:42:33Americans appreciated just how close they had come to sharing
0:42:33 > 0:42:36in what was by then a worldwide tragedy.
0:42:36 > 0:42:41Frances Kelsey was given an award by John F Kennedy,
0:42:41 > 0:42:45in recognition of her outstanding work.
0:42:45 > 0:42:48Thalidomide was eventually withdrawn
0:42:48 > 0:42:50from the worldwide market.
0:42:50 > 0:42:53The fact that this tragedy was allowed to happen
0:42:53 > 0:42:58and go on for so long, emphasises how little control many governments
0:42:58 > 0:43:02actually had over medicines just 50 years ago.
0:43:02 > 0:43:05In Britain, for example, the Arsenic Act,
0:43:05 > 0:43:07and the acts that followed it, had put existing drugs
0:43:07 > 0:43:10and chemicals under some sort of control.
0:43:10 > 0:43:13But there was still no effective regulation
0:43:13 > 0:43:15of newly discovered drugs.
0:43:16 > 0:43:20After the Thalidomide scandal, new laws were passed here
0:43:20 > 0:43:23and in other countries, which meant that in future,
0:43:23 > 0:43:25drugs had to be safe, they had to be effective,
0:43:25 > 0:43:28and doctors also had to tell their patients
0:43:28 > 0:43:30if they were being given something experimental.
0:43:30 > 0:43:33Because astonishingly enough, before then,
0:43:33 > 0:43:36a doctor could give you pretty much what he or she wanted,
0:43:36 > 0:43:38and they didn't have to tell you.
0:43:38 > 0:43:42These days, pharmaceutical companies wishing to launch a new drug
0:43:42 > 0:43:45have to go through multiple clinical trials,
0:43:45 > 0:43:49to demonstrate that their drug is safe and effective.
0:43:49 > 0:43:53It can take years and cost billions of pounds.
0:43:53 > 0:43:56But it's only by doing this sort of rigorous testing
0:43:56 > 0:44:01that you discover if a drug has significant toxic side effects.
0:44:03 > 0:44:05The broader impact of Thalidomide,
0:44:05 > 0:44:09it essentially creates eventually a gold standard
0:44:09 > 0:44:12for how drugs should be evaluated.
0:44:12 > 0:44:17Thalidomide led to much tighter regulations, which was a good thing,
0:44:17 > 0:44:20but the story of Thalidomide does not end here.
0:44:21 > 0:44:24Thalidomide seems to cause birth defects
0:44:24 > 0:44:27by blocking the creation of new blood vessels.
0:44:27 > 0:44:31Growing limbs are particularly vulnerable.
0:44:31 > 0:44:34It is clearly a very dangerous drug.
0:44:34 > 0:44:39Yet this notorious chemical has been found to have beneficial effects.
0:44:42 > 0:44:46For example, when it was given to people with Leprosy,
0:44:46 > 0:44:48their skin lesions turned from this...
0:44:50 > 0:44:53..to this, literally overnight.
0:44:55 > 0:44:58And it's also being successfully used
0:44:58 > 0:45:02on a particularly hard to treat form of cancer, multiple myeloma.
0:45:04 > 0:45:06The rise and fall and rise again of Thalidomide
0:45:06 > 0:45:10illustrates just how tricky medical research can be.
0:45:10 > 0:45:14In one context a drug could be a poison, in another a life-saver.
0:45:33 > 0:45:36Despite the challenges, and with tighter regulations in place,
0:45:36 > 0:45:39medical research continues apace.
0:45:40 > 0:45:44While some still focus on mineral and plant poisons
0:45:44 > 0:45:45or build synthetic ones,
0:45:45 > 0:45:48others are now driving forward,
0:45:48 > 0:45:50into the dangerous world of the microbe.
0:45:53 > 0:45:55Although they are only microscopic,
0:45:55 > 0:45:58microbes can produce toxins which are real heavyweights.
0:45:59 > 0:46:03And the ultimate microbial poison we have purified and tamed,
0:46:03 > 0:46:07is a toxin produced by the microbe Clostridium botulinum.
0:46:11 > 0:46:16Botulinum toxin is the most poisonous substance known to man.
0:46:16 > 0:46:20Now, a couple of teaspoons full would be enough to wipe out
0:46:20 > 0:46:23every person in the UK.
0:46:23 > 0:46:26And a couple of kilos would kill every human on the planet.
0:46:29 > 0:46:31Fortunately, this is sugar,
0:46:31 > 0:46:33but I do have some botulinum toxin -
0:46:33 > 0:46:36better known as Botox - over here.
0:46:36 > 0:46:41Only a few nanograms, but it is botulinum toxin none the less.
0:46:41 > 0:46:44The toxin is produced by bacteria,
0:46:44 > 0:46:49and was first discovered in poorly prepared sausages during the 18th century.
0:46:49 > 0:46:52It was named after the Latin for sausage, botulus.
0:46:55 > 0:46:58On the LD50 toxicity scale,
0:46:58 > 0:47:05Botox measures just 0.000001 milligrams per kilogram.
0:47:07 > 0:47:10The deadliest of the deadly.
0:47:10 > 0:47:15A lethal dose for me, weighs less than one cubic millimetre of air.
0:47:16 > 0:47:19Botulinum toxin, like curare,
0:47:19 > 0:47:23commonly kills its victims by causing respiratory failure.
0:47:23 > 0:47:26But unlike curare, you're not going to be able to keep someone alive
0:47:26 > 0:47:28with a pair of bellows.
0:47:28 > 0:47:31Because botulinum toxin lasts much longer.
0:47:31 > 0:47:35You have to keep them on a ventilator for weeks, if not months.
0:47:37 > 0:47:43Botox works by preventing muscles from receiving nerve signals.
0:47:46 > 0:47:51Botox is an enzyme which enters the nerve and destroys vital proteins.
0:47:53 > 0:47:56This stops the communication between nerves and muscles.
0:47:57 > 0:48:01Only the growth of new nerve endings can restore muscle function,
0:48:01 > 0:48:03and this can take months.
0:48:06 > 0:48:10Botox is a neurotoxin, which means it destroys nerves.
0:48:10 > 0:48:14Oddly enough, that makes it useful for a number of medical conditions
0:48:14 > 0:48:18ranging from eye squints, to migraines,
0:48:18 > 0:48:22from excess sweating, to leaky bladders.
0:48:22 > 0:48:27But its main use, of course, is ironing out wrinkles in ageing faces
0:48:27 > 0:48:31and it does this by destroying the nerves that cause frowning.
0:48:32 > 0:48:35The quantities used are absolutely tiny,
0:48:35 > 0:48:38a few billionths of a gram dissolved in saline.
0:48:40 > 0:48:45In the name of science, I tried botox a few years ago.
0:48:45 > 0:48:47- It wasn't painful, was it? - No, no.
0:48:49 > 0:48:52It certainly smoothed away the wrinkles.
0:48:52 > 0:48:55But it also gave me a weird expression
0:48:55 > 0:48:57until the new nerve endings grew back.
0:49:00 > 0:49:02It may not be to everyone's taste,
0:49:02 > 0:49:04but botox is certainly big business.
0:49:04 > 0:49:08Costing around a hundred trillion pounds per kilo,
0:49:08 > 0:49:11botox is the most expensive product on earth.
0:49:27 > 0:49:31Huge amounts of money can clearly be made from new medicines,
0:49:31 > 0:49:35so it's no wonder that the search for them continues.
0:49:35 > 0:49:38Having started out by collecting exotic poisons,
0:49:38 > 0:49:42extracted from plants, such as curare, we've come full circle.
0:49:43 > 0:49:47As well as microscopic life, researchers are intensely
0:49:47 > 0:49:53interested in studying some of the other ingenious killers of the natural world.
0:49:53 > 0:49:57Killers that scuttle, slide and slither.
0:50:05 > 0:50:12In this room there are over 250 snakes, spiders, scorpions and other venomous creatures.
0:50:13 > 0:50:16Their venoms have evolved over millions of years
0:50:16 > 0:50:19and they're all different.
0:50:27 > 0:50:29The hope is that amongst this lot,
0:50:29 > 0:50:33there are some which could lead to a significant medical breakthrough.
0:50:35 > 0:50:39One of the greatest medical challenges is still cancer -
0:50:39 > 0:50:42particularly, cancers of the brain.
0:50:42 > 0:50:46Brain tumours like this one here, can be quite difficult to treat.
0:50:46 > 0:50:52If you use radiotherapy, chemotherapy, you risk damaging healthy tissue.
0:50:52 > 0:50:55If you can get at it and cut it out then that's good,
0:50:55 > 0:50:58but also it's quite difficult sometimes to tell the difference
0:50:58 > 0:51:01between tumour and healthy tissue.
0:51:04 > 0:51:09Surgeons face a real dilemma in how much of the surrounding tissue they should remove.
0:51:11 > 0:51:15Even though on a scan you may see a tumour,
0:51:15 > 0:51:18that looks let's say 2cm in size,
0:51:18 > 0:51:23we know that there are tumour cells several centimetres away
0:51:23 > 0:51:25from that ball of tumour.
0:51:25 > 0:51:29So to entirely remove everything you would need to be able to remove
0:51:29 > 0:51:32all that surrounding tissue, most of which is normal brain.
0:51:33 > 0:51:35Removing healthy brain tissue
0:51:35 > 0:51:39could mean the difference between walking and not walking,
0:51:39 > 0:51:41seeing and not seeing,
0:51:41 > 0:51:43talking or being mute.
0:51:43 > 0:51:47And so being able to pinpoint unhealthy tissue, is critical.
0:51:47 > 0:51:51Which is where venomous animals may be able to help.
0:51:53 > 0:51:58This is Leiurus quinquestriatus, also known as the death stalker.
0:51:58 > 0:52:02As her name implies, she is a particularly venomous scorpion.
0:52:02 > 0:52:05A single sting from that tail
0:52:05 > 0:52:07could probably kill a child or an elderly person,
0:52:07 > 0:52:09although probably not kill me,
0:52:09 > 0:52:13it would certainly be excruciatingly painful.
0:52:13 > 0:52:18The venom of this scorpion contains a powerful cocktail of neurotoxins,
0:52:18 > 0:52:21chemicals that poison brain cells and nerve cells.
0:52:25 > 0:52:28One, is called chlorotoxin.
0:52:30 > 0:52:33Chlorotoxin affects the nervous system of insects,
0:52:33 > 0:52:35utterly paralysing them.
0:52:36 > 0:52:38But when trialed in human tissue,
0:52:38 > 0:52:41it did something completely different.
0:52:41 > 0:52:44It seemed to have a special affinity for cancer cells.
0:52:46 > 0:52:50The compound bound to the tumour, and avidly bound -
0:52:50 > 0:52:53in other words, once it's stuck, it stayed stuck.
0:52:56 > 0:53:00Chlorotoxins from the scorpion venom bind tightly to receptor sites
0:53:00 > 0:53:02on the surface of the cancer cells.
0:53:02 > 0:53:05These are called Annexin A2.
0:53:05 > 0:53:10Unfortunately the chlorotoxin is not strong enough to actually kill the cancer cell.
0:53:10 > 0:53:13However, when it's mixed with a fluorescent dye,
0:53:13 > 0:53:16it highlights cancer cells,
0:53:16 > 0:53:19allowing surgeons to avoid cutting out healthy brain tissue.
0:53:22 > 0:53:27It can be visually extremely difficult to differentiate tumour
0:53:27 > 0:53:31from normal brain, they look alike they can feel alike.
0:53:31 > 0:53:35So the ability to fluorescently identify areas that are abnormal
0:53:35 > 0:53:37based on the fact that they bind chlorotoxin,
0:53:37 > 0:53:41and then remove that tissue, is extremely appealing.
0:53:41 > 0:53:46So in the operating room, we would simply switch our imaging system
0:53:46 > 0:53:49to a system that shines infra-red light,
0:53:49 > 0:53:52and just look at the picture we see.
0:53:53 > 0:53:56The areas that light up blue, should be just tumour,
0:53:56 > 0:54:00so you can detect microscopic amounts of tumour.
0:54:01 > 0:54:02It's promising research,
0:54:02 > 0:54:06and just one area where this venom could offer medical benefit.
0:54:08 > 0:54:10It's been a long process and development,
0:54:10 > 0:54:13lots of twists and turns
0:54:13 > 0:54:17but, yeah, I'm looking forward to where the future goes with this.
0:54:17 > 0:54:21It certainly has the potential to be very, very promising.
0:54:25 > 0:54:28Animals produce a huge range of different venoms,
0:54:28 > 0:54:32and many have been shown to have remarkable properties.
0:54:35 > 0:54:41Venom from snakes has led to the production of a new type of anti-hypertensive drug,
0:54:41 > 0:54:43for treating high blood pressure,
0:54:43 > 0:54:46while the lethal cone snail
0:54:46 > 0:54:49has produced one of the world's most powerful painkillers.
0:54:50 > 0:54:55So who knows what other medicines might be lurking in the fangs of the creatures behind me?
0:54:59 > 0:55:02Venoms are particularly appealing to modern researchers,
0:55:02 > 0:55:05because they tend to be very specific.
0:55:05 > 0:55:08They seek out precise targets,
0:55:08 > 0:55:12which ties in well with another medical revolution that's going on.
0:55:14 > 0:55:17It, too, builds on the idea of targeting -
0:55:17 > 0:55:21but this time it's targeting at a genetic level.
0:55:23 > 0:55:25Medicine is getting truly personal.
0:55:27 > 0:55:30The trouble with dishing out the same drugs to everyone,
0:55:30 > 0:55:32is that we are all different,
0:55:32 > 0:55:37a drug that lowers my blood pressure might have absolutely no effect on yours.
0:55:37 > 0:55:41So how close are we to creating truly personalised medicines?
0:55:43 > 0:55:47What we've found as we've sequenced the genes of a number of people,
0:55:47 > 0:55:51is that everybody has slight variations and subtle changes
0:55:51 > 0:55:52in their genes,
0:55:52 > 0:55:55and these dictate ever-so-slightly subtle differences
0:55:55 > 0:55:58in the way that cells respond to drugs.
0:55:58 > 0:56:01The concept is that we use that information
0:56:01 > 0:56:05to really tailor a specific therapy for that one person.
0:56:10 > 0:56:13We're doing it to some extent already.
0:56:14 > 0:56:21Right now, we can sequence relevant bits of the person's cancer genome,
0:56:21 > 0:56:25for about the same cost as many of the scans we do for patients with cancer.
0:56:25 > 0:56:29The similar sort of cost as the pathologist looking down the microscope
0:56:29 > 0:56:32at the slides from that person's cancer.
0:56:32 > 0:56:37So I think it's very likely that over the next 5 to 10 years or so,
0:56:37 > 0:56:41these kinds of genetic approaches will make their way into the clinic.
0:56:46 > 0:56:50Personalised medicine is set to be the next big step
0:56:50 > 0:56:53in a process that started in the early 19th century.
0:56:56 > 0:57:00Since that time, our medical world has been utterly transformed.
0:57:00 > 0:57:03We no longer expect to die young,
0:57:03 > 0:57:09instead the threat comes from diseases of old age like cancer.
0:57:09 > 0:57:12Here poisons have proved to be particularly useful.
0:57:13 > 0:57:15Even arsenic, the murderer's friend,
0:57:15 > 0:57:19has now found a medical use, as an anti-cancer agent.
0:57:22 > 0:57:27Thanks to medical pioneers, we now know how to control pain,
0:57:27 > 0:57:31infections are not the death sentence they once were.
0:57:33 > 0:57:36And doctors use many poisons on a daily basis.
0:57:44 > 0:57:47200 years ago, there were very few effective treatments.
0:57:47 > 0:57:53Now, doctors are talking about targeted, specific, personalised medicines.
0:57:53 > 0:57:57We have come a long way, but we still have a long way to go.
0:58:06 > 0:58:09If you'd like to take part in a quiz on pain,
0:58:09 > 0:58:13or perhaps find out something more about pus and poison,
0:58:13 > 0:58:15then go to the website below
0:58:15 > 0:58:18and follow links to the Open University.
0:58:20 > 0:58:24Subtitles by Red Bee Media Ltd