Botulinum Toxin: Lethal Weapon or Magic Bullet?

Like penicillin botulinum toxin could become a legend. Until recently, the toxin wasknown primarily as the cause of botulism, a type of deadly food poisoning produced byimproper canning. In the late 1980s, Canada approved use of the toxin to treat strabismus(also known as cross-eyes), and Americans suffering from this ailment began crossing theborder for medical relief. In 2001, Canada approved an additional use for the toxin--theremoval of facial wrinkles--and in 2002, the FDA in the United States followed suit. (1,2). Subsequently, the neurotoxin has become a household name as clients line up at localgyms, parties, and spas for their quarterly Botox injections, in order to temporarily ridthemselves of wrinkles and sweaty armpits. The toxin now enjoys a type of celebritycache, for better or worse, and has been featured comically on popular sit-coms andcomic strips (3-8). Profits are expected to hit an all time high as the toxin makes the leap from therapeuticdrug to beauty aid, and this financial trend is likely to grow, since a number of newtherapeutic applications may be developed and approved for use in the next few years.Dr. Mitchell F. Brin, vice president of Allergan, claims that botulinum toxin type A couldtreat up to ninety-three human disorders (5, 9). Meanwhile, Elan pharmaceuticals hassecured rights to specific clinical applications of botulinum type B (10). Both companieshope to secure a unique financial niche, and scientific investigations of botulinum toxinaction suggest that the versalitity of the toxin will make this possible. By investigatinghow the toxin goes about disrupting neurological function, scientists have begun to learna great deal about the basic properties of neuronal transmitter release and cellularsecretion pathways (11-14). These findings may lead to new treatments for neurologicaland endocrine disorders such as cerebral palsy, Parkinson's Disease, Graves Disease, andCushing's Disease (9, 15-17). Perhaps most surprising is that the lethal toxin is beingengineered as a delivery vehicle for oral vaccines such as those used for cancer (18). Sothe stakes are very high--both for those who suffer from debilitating diseases and thepharmaceutical companies who will develop and sell the medical applications. There is also another side to this story, which is perhaps not as well known, but is just asimportant: namely, the use of the toxin as a lethal agent. Clostridium botulinum is thebacterium that produces the world's most deadly toxin. A small dose of the toxin can kill10 million people within 48 hours. If aerosolized, the bacterial spores linger in the air forup to two days. These spores germinate once they have entered a human host and, if theconditions are right, begin to release the neurotoxin (13, 19, 20). With potency 10,000 times stronger than any other biological poison, the botulinum toxinwas recruited as a biological weapon many years ago, and it continues to be used today.During WWII, Stanley Lovell, an American officer in the Office of Strategic Services,ordered the manufacture of gelatin capsules containing the toxin. The plan was forChinese prostitutes to hide these capsules behind their ears and then slip them into themeals of high-level Japanese officials(20). More recently, in 1993 the Iraqi leader

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.