[MUSIC] Okay, opium is a material that has been used since ancient times, particularly for its medicinal properties, for instance, as a painkiller. And opium is the crude material that's obtained from the seed heads of the poppy, papaver somniferum. Somniferum is Latin for bringer of sleep, and one of the effects of taking opium is to become sleepy, so it would help people sleep. The way opium was obtained is that the seed heads are scored and the latex exudes from those cut marks, and that latex, when it's dried, is opium. Paracelsus, who we'll meet again in a lecture on toxicology, went one better - he improved opium by extracting it with alcohol, and this gives a liquid, which was given the name laudanum, and that was used medicinally. In most countries, of course, opium production is illegal. Currently, the major illegal producer of opium is Afghanistan. Other countries that produced opium in the past, such as Burma and Thailand and Laos, now produce much less of the stuff. Now, what is it in opium that has these effects? And the answer is, it is a chemical called morphine. So we can say that morphine has been used as a painkiller for thousands of years, and in fact, it is still used as a painkiller, and even today, it is one of the most effective. So because there is still clinical demand for morphine, there not only are the illegal producers, there's also the legal producers. And the biggest legal producer is in fact the Australian State of Tasmania, and opium poppies are grown in fields in Tasmania, which apparently causes some problems for the local wallabies. One of the uses of opium is for gastrointestinal problems. So if you have a bad stomach upset, you have eaten something you really shouldn't, one way to cure those problems is by taking opium, and opium was used in this way up to a few decades ago. Even when I was a child, when I had a stomachache, my parents would give me a spoonful of something called kaolin, and morphine, and I can tell you, it tastes disgusting. Now, one thing you learn after having a spoonful of kaolin and morphine is to be careful what you eat in future. One person who we know took opium is the poet, Samuel Taylor Coleridge. And one of the poems that he's best known for is the poem, "Kubla Khan", which starts "In Xanadu did Kubla Khan A stately pleasure-dome decree:". According to the story, Coleridge came up with this poem while under the influence of opium, but before he could write it down, he was famously interrupted by the man from Porlock. So what we have in the poem Xanadu is only a part of what he dreamed about while he was in this influence of opium. In his own words, he says, "This fragment, with a good deal more, not recoverable, composed in a sort of Revery brought on by two grains of Opium taken to check a dysentery, at a Farm House between Porlock and Linton, a quarter of a mile from Culbone Church, in the fall of the year, 1797." Well, that was a long time ago, but even now we can still find medicines containing opium. Okay, here's a packet from some Thai stomach medicine, and if you look at the ingredients carefully, you see "Opium Tincture, 0.60 millilitres". Well, that's not very much opium; I might be a little bit more worried about the antimony potassium tartrate that's also in there. Well, opium has also inspired composers. Here's the composer Hector Berlioz, and it is believed that his Symphonie Fantastique was composed under the influence of opium. So if you want to know what it's like to take opium, but you don't actually want to take opium, you could just listen to Symphonie Fantastique. Opium has also caused wars. There were two opium wars between the British and the Chinese in the 19th century, the primary cause being trade in opium. Opium or morphine may also have affected the Second World War. Hermann Goering, who was Head of the German Airforce during that war, was addicted to morphine. He'd become addicted after his doctor had prescribed some for him, and it's possible that some of the odd decisions taken by the Luftwaffe were influenced by that addiction. So we know opium, that's what is the crude material that comes from the plant; and we know morphine, that is the active ingredient in that crude material. The third member of this trio is heroin. What is heroin? Heroin is a semi-synthetic. It was invented by a chemist working for the well-known pharmaceutical firm Bayer in Germany, and chemically it is diacetylmorphine. Bayer is also the company that gave us aspirin, and in fact, they used the same chemistry to convert morphine into heroin as to convert the starting material they were using, salicylic acid, into aspirin. They were very impressed by heroin - it made people feel strong. It was more potent than morphine, and this word "Heroin" was dreamt up by their marketing department. The idea was take heroin and feel like a hero. Of course, very quickly, the awful side effects of heroin were discovered. It was taken off the market and country after country banned it. In many countries, heroin is totally banned. In a few countries, including the United Kingdom, heroin may still be used medicinally if prescribed by a doctor. For instance, if you have a terminal cancer patient who is suffering great pain, a U.K. doctor may prescribe them heroin to ease their symptoms. The fact that heroin is available in some countries to doctors can be very unfortunate. Here's the case of Harold Shipman. He was a British family doctor and also a serial killer, and he would murder old ladies who were in his charge by administering them a lethal dose of heroin. Because all of these ladies were old, they were already in poor health, and Dr. Shipman was a respected local doctor, there was very little suspicion, and there was no investigation of him until he made a mistake. It's only when he forged a will for one of his victims that there was an investigation and he was caught. It is not known how many people Harold Shipman killed. Statistically, it's been estimated it could be well over 200 people, making him one of the most prolific serial killers of all time, and he did it with heroin. How does heroin work? Why is it better than morphine? Well, on the left you see the structure of morphine and this is treated with a chemical called acetic anhydride to convert it into heroin. Now, originally heroin meant this compound here. Nowadays, the term heroin refers to the illegal drug, which is pretty much always going to be impure. So the term used for the pure compound is the chemical term diacetylmorphine, which may be shortened to diamorphine. The chemical used for this transformation, acetic anhydride, is nowadays controlled in many of the countries where morphine is produced, and also in the nearby countries where the processing may occur. Now how does diamorphine work, why is it so much more effective than morphine? And the answer is, this derivatization of morphine result in a chemical that is transported faster through the body and into the brain. So those two acetyl groups that are added simply speeds up the transport of the molecule within the body. The two acetyl groups will be rapidly cleaved off by metabolic processes to release morphine. So the actual action on the brain is just the action of the morphine, but the faster transport to the brain means that a much higher concentration will be obtained in a shorter time. A consequence, of course, of this rapid cleavage of these acetyl groups is that if the urine, for instance, of a user is analyzed, diamorphine itself is unlikely to be detected, but morphine will be detected. Well chemists, of course, have made many, many derivatives of morphine, and some of them will have similar properties, some of them have different properties. So one analog of morphine is etorpine, and this is a very powerful tranquilizer. So if, for instance, there's a wild animal on the loose escaped from the local zoo, and it has to be shot by someone with a dart gun to make it fall asleep, then that dart would probably contain etorpine. If you've seen the Jurassic park movies, there's one of them where they tranquillize a Tyrannosaurus Rex, and they probably did that, or would have done that, with a really big dose of etorpine. Now, etorpine was discovered by a research group in a university, and there's a story about how they realized that this material was a very powerful tranquilizer. Apparently this research group would have afternoon tea together, and one day the guy whose job it was to make the tea couldn't find the spoon to stir the tea. So he took one of the spatulas or stirring rods from the lab and used that to stir the tea, but didn't realize that that stirring rod wasn't clean - it had traces of etorpine on it. So after drinking the tea, the whole research group fell asleep, and when they woke up, they realized the discovered a really potent tranquilizer. [BLANK_AUDIO] Now, back to heroin. We have said that heroin nowadays refers to the illegal drug, which will be impure and it will have all sorts of impurities in it. Some of these will be related compounds, for instance, if the acetylation reaction is not done properly, there will be left over morphine in the heroin. There may also be codeine and thebaine, and these are morphine-like alkaloids which are also produced by the poppy plant. The codeine may be acetylated in the same process by which morphine is acetylated, and therefore, acetyl codeine may also be present. So these are closely related compounds which are likely to be in the heroin sample. The poppy plant also produces other alkaloids which are not related to morphine, such as papaverine and noscapine, and these may be detected in the heroin sample too. In addition, the heroin may have been cut, that is, diluted, with inert or less active materials, such as sugar or caffeine or barbiturates. So, if a sample of heroin is seized, it can be analyzed chemically, it can be analyzed by GC or by HPLC. And the composition of different samples of heroin that have been seized can be compared, and then you can see whether the samples came from the same source, therefore they would have the same composition, or whether they come from different sources. [BLANK_AUDIO]
