Botulinum toxin: historical perspective and treatment of neurogenic and idiopathic overactive bladder

Botulinum toxin: from poison to ploughshare The term ‘botulism’ comes from the Latin word botulus, meaning ‘sausage’. The fi rst published account of the food-borne illness was traced to sausage in 1820 by German physician Christian Kerner. The symptoms of dry mouth, blurred vision, diffi culty swallowing, drooping eyelids, slurred speech, vomiting and, in some, generalized muscle weakness, are all attributable to botulinum toxin (BTX). If the respiratory muscles were affected then the disease was fatal. Kerner isolated the substance from the meat and cadavers of the victims. He then showed the isolated substance to be extremely toxic to animals. Amazingly, over 150 years before his time, he suggested this substance might be used in the future as a therapeutic agent against involuntary movements in patients with neurologic disease [1]. While this is the origin of the word botulism, this food-borne illness has likely accompanied mankind throughout antiquity. There are older case reports describing patients with dilated pupils and fl accid paralysis. These incidents were attributed to belladonna intoxication. Belladonna plant extract was commonly used to dilate women’s pupils, a trait at that time considered beautiful. It is now known that atropine, the active ingredient in belladonna, only affects parasympathetic muscarinic receptors and would not cause skeletal muscle paralysis. These older texts probably describe patients with botulism [2]. The anaerobic bacterium that produces BTX, now called Clostridium botulinum, was fi rst isolated by Emile van Ermengem, who worked in a laboratory with Robert Koch. This occurred in 1895, after an outbreak that originated from ham at a funeral in Belgium. Outbreaks of botulism continued throughout the world in the early 1900s, till improvements in canning processes were developed. In the following years, seven different antigenically distinct strains of BTX, labeled A to G, were discovered, based on their differing ability to activate antibodies [2]. The next major scientifi c discoveries regarding BTX came not from medical research, but from the military during the world wars. Biological warfare fears led military scientists on both sides to study and purify BTX. The toxin was developed by the USA and separately by the British military. Both were serotype A (BTX-A). Long after the war, these two strands of BTX-A would eventually be brand-named Botox and Dysport, respectively. These brand names are not interchangeable, as the doses are different due to differing potencies. For this reason, the brand names will be used where indicated in this Overactive bladder (OAB) affl icts nearly 17% of the population, causing frequent urgent dashes to the bathroom, sometimes with leakage along the way. This causes diffi culties with employment, as well as social and even sexual relationships. The costs of consultations, medications, physiotherapy, surgery, pads, undergarments, cleaners for carpet or furniture, catheters and the treatment of skin and bladder infections has been estimated to be US$32 billion. OAB is not a fatal disease like botulism, but those who suffer from OAB can feel as if their lives have been paralyzed by their bladders. Botulinum toxin can paralyze the bladder in turn, and has emerged as a possible treatment of this epidemic. How botulism was discovered is a testament to early scientist–physicians. The story is fascinating, and how different militaries purifi ed the toxin, a possible weapon of mass destruction, is equally frightening. The medical potential of the toxin was predicted by the very physician who discovered botulism, and the 175 clinical trials currently listed at clinicaltrials.gov attest to the conversion of this substance from killer to healer.