Pain, pus and poison.

Michael Mosley tells the extraordinary story of how scientists learnt to use the world around us to conquer the common afflictions of pain, pus and poison. In the third of three programmes, Mosley examines poisons, exploring the turning points when scientists went from finding antidotes to poison to applying poisons as a cure. Mosely begins at Walton Hall in Yorkshire, the former home of eccentric naturalist Charles Waterton. While living in the Amazon, Waterton obtained the recipe for a notorious poison with the principle ingredient curare. Together with eminent surgeon Benjamin Brodie, he proved (by experimenting on a donkey) that the poison does not kill, providing that respiration is maintained artificially. While the drug had no immediate applications at the time, it was later introduced into anaesthesia as a muscle relaxant for surgery. The uptake of in life insurance in Victorian Britain led to a surge in financially motivated murders. One of the highest profile cases was that of Mary Ann Cotton, a serial killer who murdered at least 17 before the final victim tested positive for arsenic. Laws restricting the sale of poisons ultimately helped regulate the trade of pharmacists. Mosley demonstrates the pupil dilating effects of atropine sulphate – isolated from deadly nightshade. In Prague in 1864 a local doctor discovered that another poison, the Calabar bean, could be used to reverse the effect of atropine overdose. It wasn’t long before poisons were commonly found in physicians’ drug cabinets. But WWI marked a return to their darker roots. Mustard gas was one of a number of chemical weapons developed by the Kaiser Wilhelm Institute under the directorship of Fritz Haber. On the eve of WWII, researchers at the Yale University School of Medicine were working on antidotes when they discovered that soldiers affected by mustard gas had low white blood cell counts. The group went on to experiment successfully with nitrogen mustard as a treatment for Hodgkin's lymphoma – the first use of chemotherapy. Paracelsus famously claimed that ‘all substances are poisonous’. The 16th century physician realised that it is simply the dose which determines toxicity. Although toxicity varies according to the species and type of exposure, it is useful to have a comparative scale. One measure is the LV50; how much of a substance is needed to kill half of those who take it. Dosages are per kilogram of body mass; substances with an LV50 of less than 100mg per kilo are typically labelled poisons. Moving on to medicines that have proved poisonous, Mosely recalls the thalidomide crisis of the 1960s. Thalidomide was prescribed for morning sickness but resulted in severe birth defects; it is estimated that 10,000 babies were affected. Although widely used in Europe and Australia, the drug was repeatedly refused FDA approval in America. After the scandal, new laws were passed making clinical trials mandatory. Thalidomide has since been used to treat leprosy and cancer. Microbes produce the most poisonous (and expensive) substance known to man – botulinum toxin, better known as Botox. Two kilos would be enough to kill everyone on the planet. Because it destroys nerves, it has proved useful for treating a range of medical conditions from migraine to excess sweating. Mosely discusses the clinical uses of venom briefly. Chlorotoxin from the deathstalker scorpion binds preferentially to brain cancer cells. When mixed with a florescent dye, it helps surgeons excise tumour from healthy tissue. Concluding with a look at the future of personalised medicine, Peter Campbell from the Wellcome Trust Sanger Institute discusses genetically targeted cancer drugs.