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The botulinum neurotoxins are the most toxic substances known; they are one million times more toxic than the cobra toxin. In spite of their extreme toxicity there has been a rapid expansion of the medical applications for the botulinum neurotoxins, with new applications constantly being discovered. This line of treatment is becoming the standard procedure for many conditions. The toxins are possible agents for bioterrorism and the development of countermeasures and vaccines are of high priority. We are studying the toxins using a wide variety of methods, including X-ray crystallography and cryo-EM to understand the toxins basic mechanism and to improve their therapeutic properties.