The timeline of botulinum toxin discovery began with deadly outbreaks related to contaminated food across Europe in the late 1700s, the largest of which occurred in 1793 in Wildebrad, in southern Germany. In 1811, “prussic acid” was named as the culprit in what was referred to as sausage poisoning. Between 1817 and 1822, German physician Justinus Kerner noted that the active substance interrupted signals from motor nerves to muscles, but spared sensory and cognitive abilities, accurately describing botulism. He hypothesized that this substance could possibly be used as treatment for medical conditions when ingested orally. It wasn’t until 1895 that microbiologist Emile Pierre Van Ermengem, a professor of bacteriology in Belgium, identified the bacterium responsible as Bacillus botulinus, later renamed C. botulinum.
In 1905, it was discovered that C. botulinum produced a substance that affected neurotransmitter function, and between 1895 and 1915, seven toxin serotypes were recognized. In 1928, Herman Sommer, PhD, at the Hooper Foundation, at the University of California, San Francisco, isolated the most potent serotype: botulinum toxin type A (BoNT-A).
Dr. Naissan O. Wesley
In 1946, Carl Lamanna and James Duff developed concentration and crystallization techniques that were subsequently used by Edward Schantz, PhD, at Fort Detrick, Md., for a possible biologic weapon. In 1972, Dr. Schantz took his research to the University of Wisconsin, where he produced a large batch of BoNT-A that remained in clinical use until December 1997.
In the late 1960s and early 1970s, an ophthalmologist in San Francisco, Alan Scott, MD, began animal studies with BoNT-A supplied by Dr. Schantz, as a possible treatment for strabismus, publishing his first report of BoNT-A in primates in 1973. In 1978, the Food and Drug Administration granted approval to begin testing small amounts of the toxin in human volunteers. In 1980, a landmark paper was published demonstrating that BoNT-A corrects gaze misalignment in humans. By 1989, it was approved as Oculinum by the FDA for the treatment of strabismus and blepharospasm.
Keen clinical observation and a serendipitous discovery led to botulinum toxin’s first uses for cosmetic purposes. In the mid-1980s, Jean Carruthers, MD, an ophthalmologist in Vancouver, noted an unexpected concomitant improvement of glabellar rhytids in a patient treated with BoNT for blepharospasm. The result of the treatment was a more serene, untroubled expression. Dr. Carruthers discussed the observation with her dermatologist spouse, Alastair Carruthers, MD, who was attempting to use soft tissue–augmenting agents available at the time to soften forehead wrinkles. Intrigued by the possibilities, the Carruthers subsequently injected a small amount of BoNT-A between the eyebrows of their assistant, Cathy Bickerton Swann, also now known as “patient zero” and awaited the results.
Seventeen additional patients followed, aged 34-51, who collectively, would become part of the first report on the efficacy of BoNT-A for cosmetic use – for the treatment of glabellar frown lines – published in 1992.
Between 1992 and 1997, the popularity of off-label use of BoNT-A grew so rapidly that Allergan’s supply temporarily ran out. By 2002, safety and efficacy profiles of use in medical conditions such as strabismus, blepharospasm, hemifacial spasm, cervical dystonia, cerebral palsy, poststroke spasticity, hyperhidrosis, headache, and back pain had been well-established, facilitating the comfort and use for cosmetic purposes.
By 2002, open-label studies of more than 800 patients confirmed the efficacy and safety of BoNT for the treatment of dynamic facial rhytids. And in April 2002, the FDA granted approval of BoNT for the nonsurgical reduction of glabellar rhytids. The rest, some would say, is history. On this 20th-year anniversary of the approval of botulinum toxin for cosmetic use, special recognition is given here for the physicians and scientists who were astute enough to make this discovery, as botulinum toxin use remains one of the most popular and effective nonsurgical cosmetic procedures today.
Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at dermnews@mdedge.com. Dr. Wesley disclosed that she has been a clinical investigator and consultant for Botox manufacturer Allergan in the past, and manufacturers of other brands of botulinum toxins available for cosmetic use; Dysport (Galderma), Xeomin (Merz), and Jeuveau (Evolus). Dr. Talakoub had no disclosures.
Reference
“Botulinum Toxin: Procedures in Cosmetic Dermatology Series 3rd Edition” (Philadelphia: Saunders Elsevier, 2013)