[MUSIC] Well, we've been talking about poisons, but we haven't actually defined a poison. So lets give a definition of a poison. We can say a poison is any substance, which if taken into or formed in the body, destroys life or impairs health. But that's quite a straight forward definition of a poison. Now, we consider that the first toxicologist, the founder of toxicologist, was this man here, Philippus Aureolus Theophrastus von Hohenheim, who lived in the first half of the 16th century. Now, that's quite a mouthful of a name, so typically, he went by the pseudonym, Paracelsus. And Paracelsus was the first person to really think scientifically about poisoning. Paracelsus is also a medicinal chemist, and he realized that many substances that are poisonous can also be medicines. In particular, he was very fond of using mercury, and he made a very, very good point. He said that all substances are poisons, there is none which is not a poison, but he pointed out that it is the right dose that differentiates a poison from a remedy. And he was absolutely right. All substances are poisons, even a substance as common as water. Well, poisoning by water is not common, but every so often, there is a case. The thing is that to be poisoned by water, you need to drink a lot. About seven liters is probably the lethal dose for water. So a few years ago, a California radio station, KDND in Sacramento, decided to have a competition. And the title of this competition was, Hold Your Wee for a Wii. And the idea was to see how much water people could drink without going to the bathroom, and whoever could drink the most would win one of these game stations. Well, this unfortunate lady here, Jennifer Strange, really wanted to win one of these things to give to her children, so she took part in this contest. And she probably drank about 7.5 liters of water. And then after the contest, she drove home. She apparently didn't feel well, so she went to bed, and later she was found dead. Well, of course, this was the United States, so quite rightly, her family sued the radio station, and they were awarded compensation to the tune of $16 million US. What is interesting is that Jennifer Strange didn't win the contest, she came second. The winner of the contest was a lady called Lucy Davidson. And she survived, and she said this. I didn't know what was wrong with me. I just knew I had never felt so sick in my life. So there you go. All substances are poisonous, including water. Well, here's another example. This is a wild plant that grows in Europe. It grows in the woods. People grow it in their gardens. It's very common, it looks very nice. It is called the foxglove, and it's poisonous. It contains a chemical called digitalin, which is a potent heart stimulant. So if you eat too much of foxglove, your heart will be overstimulated, and you'll die. But the same chemical, digitalin, which is contained in the foxglove, is in clinical use. If someone's heart is failing, they will be given a controlled dose of digitalin, and the heart will beat properly, and their life can be saved. So just as Paracelcus said, the difference is the dose. So nowadays, we talk about dose response curves. So if we have a particular substance in a low dose, there's no response. The body can handle it, there's no effect. If the dose is increased, then we start to get mild toxicity, some illness. Further increase, we will get severe toxicity where the person is very ill and suffering. And then above a certain dose, of course, this will lead to death. So this is a typical kind of dose response curve. Of course, the steepness of the curve, how soon it leads to death, is going to be very, very variable depending on the chemical. You need seven liters of water, at least, in order to kill somebody. But for some chemicals, you may only need milligram amounts. So how do we measure toxicity? The number we use is called the LD50. This is the lethal dose for 50%. It is the amount of chemical that has to be administered to kill half the population of a given set of test animals. So suppose we have a group of mice, and we dose them with this poison, until half of them drop dead, and then we found the LD50. Now, how accurate is LD50? Well, the answer is, not very. For a start, LD50s will vary according to how you administer the poison. Orally administered poison versus injected, straight into the bloodstream, is going to be different. Further, the LD50 is going to depend on the species you use for the test. So typically, this is done on animals like mice or rats. And then we take those LD50 values for those creatures, and we assume that the LD50 for human beings is going to be something like that, but it's not necessarily so. Take the case of chocolate. Most people are well aware that chocolate is poisonous to dogs. You shouldn't give chocolate to your pet dog, because it's going to make him ill. And yet, consider human beings. I know some human beings for whom chocolate is actually an essential nutrient. So, quoted LD50 values are not scientifically firm and precise. They are a guideline, but it's the best we've got. So here are some typical LD50s for a range of poisons going from sodium cyanide right through to the botulism toxin. And the units In which LD50s are quoted are typically milligrams per kilograms, or here, micrograms per kilograms. And that is because we must always measure the dose per unit body weight. Obviously, if you're testing it in mice, mice are very small, much smaller than a human being. So you need a tinier dose for a mouse than for a human just because of the difference in size, so LD50s are always quoted per unit body weight. So size affects how much poison is lethal. Age also has an effect. Small children are easier to poison than adults simply because their metabolism is not fully developed. Older people are also easier to poison, because metabolism changes with age. The state of someone's health also has an effect, in particular, the condition of someone's liver. Someone with liver disease is going to be more susceptible and we'll see why that is in a moment. History is important, and this is because the body can develop tolerance to certain poisons. And we'll see an example of this later when we talk about arsenic. But another example would be, for instance, a heroin addict. Suppose you have someone who is injecting heroin habitually. In order to get the same high, they typically have to keep increasing the dose they inject. Now, heroin is very, very toxic. But as they gradually build up the dose they're taking, their body builds up a tolerance of heroin, so they can inject a dose of the stuff that would kill a normal person. Now, suppose that heroin addict is then arrested and goes to prison, spends some time in prison where he doesn't have any access to heroin, and then he comes out of prison, and the first thing he does is give himself a dose of heroin. Now, while he's not been exposed to the stuff in prison, he could well have lost his tolerance. So when he comes out, gives himself his normal dose, it kills him, because his tolerance have gone. And then, the human body is a very, very complex thing, and we sometimes see what are called paradoxical reactions. And this is where the body reacts to a substance, which is actually not considered poisonous, but it leads to their death. An example is the anti-malarial medicine, Lariam. If you go to a part of the world where malaria is endemic, then typically, your doctor will advice you to take a substance such as Lariam just in case you get bitten by one of the parasite-carrying mosquitoes. But Lariam is well-known that it can cause side effects. In some people, there are no side effects. I never got any side effects when I took Lariam, but it's well-known that some people go into depression caused by Lariam. And sometimes, that depression can be extremely bad. So here's a case. A student called Vanessa Brunt, very, very smart, had a place at our good university all lined up. But she took a year off, and she went to South China to teach English. And she went to a part of South China where malaria is endemic. And so following advice, she took Lariam, and it caused an extreme depression, which lead to her suicide. So if you're travelling to one of these places, then you have to balance out the risks. What's the risk of getting malaria versus the risk of a paradoxical reaction?
