Matthews Gwynn, October 2006

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BOTOX $99

That’s what the cheesy sign outside the Florida doctor’s office advertised.  I saw it in the newspaper the day after four people began hanging onto life through ventilators.  The physician injector, who had previously lost his license because of narcotics violations, was lying next to his girlfriend in Florida, while two others were doing the same in New Jersey.  Although not apparent at the time, it seems that when he couldn’t obtain the legitimate toxin from the manufacturer, he bought some veterinary-grade botulinum toxin from Arizona, at 100,000 times the potency of Botox, and injected it into the foreheads of everyone at his bargain price–even himself.  Within four days every cholinergic nerve ending in their bodies was shut down, unable to release the acetylcholine necessary to contract nearly all their striated and smooth muscles, resulting in flaccid paralysis and gastrointestinal shutdown.  Eventually, the botulism ran its course, and each of them was transferred to rehab facilities, including the doctor and his girlfriend to Shepherd Spinal Center.  I’m not privy to the final outcome, but I expect the bargain savings he got for the fake Botox won’t cover the attorney fees, fines, and lost income during his future incarceration.

When I read the news story this past year I groaned.  For half a decade I had battled the public association of Botox with Hollywood shallowness and vanity.  Now there was another detracting account about a greedy doctor preying on human foibles for sleazy gain.  It was about that time I decided to do what my wife had encouraged for a while and give up my coveted email address, botoxdoc@aol.com (but then get the even better one, braindoc@earthlink.net).

In fact, the medical history of botulinum toxin is fascinating.  According to information from the Botox manufacturer, Allergan Pharmaceuticals, Clostridium botulinum was first identified in the late 1890s, and botulinum toxin was first identified in 1895 as the causative agent in the food-borne illness that became known as botulism.  In the 1920s a crude form of botulinum toxin type A was isolated by Dr. Herman Sommer and his colleagues at the University of California. Other scientists conducted further purification studies over the next 20 years. Then during World War II the Allies were concerned about countering German biological warfare efforts, and in 1944 Dr. Edward Schantz began investigations with botulinum toxin. With the war’s timely end, interest in the toxin waned.  But then in the late 1960s, Dr. Alan Scott, an ophthalmologist, sought a substance that could be used to weaken eye muscles as an alternative to surgery for patients with strabismus. Dr. Schantz provided him with several substances to test, one of which was botulinum toxin type A, and in 1978 Dr. Scott initiated the first tests of botulinum toxin type A in humans for the treatment of strabismus. When he found success, he patented its use for this and sold the patent to Allergan, an eye care company, which licensed the product under the name Oculinum.  Because botulinum toxin is a biological product, not a synthetic medicine, patents on the substance itself cannot be obtained (although the manufacturing process and the purified product are registered and protected).  Rather, Allergan began the creative endeavor to imagine all the medicinal uses for the toxin and patent them.  Hundreds have been obtained, and those that others have raced to get before them, Allergan bought at great prices.  Thus a few inventive physicians have made millions by simply registering the use of botulinum toxin for wrinkles, sweating, headaches and dozens of other potential ailments.

There exist seven botulinum toxin serotypes, A through G.  Of these only A, B, and F have significant effects on humans, and of these only two are clinically relevant.  Serotype A is sold only as Botox in the US and as Botox and Dysport elsewhere.  Serotype B is Myobloc and arrived on the scene later.  Type F is not commercially sold and acts so briefly–about a week–that its clinical relevance is dubious.  The other types have their relative strengths and weaknesses, which are debated vigorously among professionals, but Botox has the greatest body of investigation, in part because of the vigor that its manufacturer has displayed in clinical research.

It is believed that, except for its brief hoarding by a certain bushy-mustached despot in the Fertile Crescent, the largest depot of botulinum toxin resides in California and is the source of all the Botox vials in the world.  Soon after its acquisition of Oculinum, Allergan changed the name to Botox and sought broader indications for this curious substance.  As the most obvious effect was muscle paralysis, the first candidate conditions were disorders of excessive muscle contraction.  Hemifacial spasm was quickly shown to be a tremendous conquest.  This formerly utterly frustrating oddity is now almost universally controlled with small doses of toxin. Likewise, blepharospasm had been an exasperating entity, refractory to nearly all medications.  The functional blindness is disabling.  An early FDA indication has brought many lives towards normality.  Focal dystonia, especially of the neck—also known as spasmodic torticollis—had also been a devastating condition refractory to almost any intervention.  Although under diagnosed, cervical dystonia has ruined many lives through its painful and embarrassing distortions.  There is no dissent that botulinum toxin is the preferred treatment for most cases of this disease, and the most grateful patients I treat are those that have found relief for the first time, often after having lost all hope.  .  Finally, last year Botox received approval for axillary hyperhidrosis, another underappreciated quirky but disabling condition that is greatly helped through the antimuscarinic effects on the post-ganglionic, acetylcholine-containing, sympathetic nerve endings at sweat glands.  So in the two decades after its release, the first five indications for Botox were all purely medicinal and life-changing.  In fact we are hard-pressed to identify any medicine that has made such a wonderful improvement in the quality of the lives of patients with chronic diseases.

Which is why I am flummoxed by the press’ obsession with Cosmetic Botox. This sixth indication is by far the least important to society and our patients.  Yet in the late 90’s we couldn’t get away from 20/20 or E! reports of this or that narcissistic celebrity’s testimonials to the fountain of youth.  While I too find Botox to be a delightful little revenue enhancer and a truly effective eraser of hyperkinetic lines, I am sorry that we have not more fully espoused its more beneficial side.  And the three greatest targets of current concern–spasticity, headache, and myofascial pain–offer perhaps the greatest potential rewards yet in the odyssey of this remarkable product.

Botulinum toxin, the most potent deleterious molecule known, has sometimes been called “the poison that heals.”  Although there may be four dissenters recuperating somewhere on the East Coast, many others with perfectly wrinkled foreheads adamantly agree.

Matthews Gwynn, MD
Atlanta Neurology

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