3 History of cosmetic botulinum toxin
Summary and Key Features
• In the mid-eighties, Dr Jean Carruthers noticed a concomitant improvement in glabellar rhytides in a patient treated with botulinum toxin (BoNT) for blepharospasm
• First trial involved 18 patients and was published in 1992
• By 2002, open-label studies of more than 800 patients confirmed the efficacy and safety of BoNT in the treatment of hyperfunctional wrinkles
• In April 2002, the Food and Drug Administration (FDA) approved BoNT for the non-surgical reduction of glabellar rhytides
• Cosmetic BoNT is now used for hyperkinetic lines in the face, neck, and chest, for facial sculpting, and as an adjunct to other rejuvenating modalities
• The original formulation of BoNT has since gone on to receive approval for 20 indications in more than 75 countries
Introduction
The discovery of ‘sausage poison’ and subsequent identification of Clostridium botulinum as the bacterium responsible has had an enormous and lasting impact on the field of cosmetic dermatology. As is often the case in medicine, a series of serendipitous discoveries – coupled with astute clinical observations – unlocked the potential of botulinum toxin (BoNT) and led to significant medical gains (Tables 3.1 and 3.2). Once hailed as a promising breakthrough for a handful of muscular disorders, BoNT has since become a veritable mainstay of the cosmetic practitioner, its popularity growing exponentially to become one of the most requested procedures in facial rejuvenation.
| Late 1700s | Outbreaks of deadly illness from contaminated foods sweeps across Europe |
| 1793 | Biggest outbreak in Wildebrad, Southern Germany |
| 1811 | ‘Prussic acid’ named as culprit in sausage poisoning |
| 1822 | Dr Justinus Kerner publishes monograph of ‘sausage poison’ and accurately describes botulism |
| 1895 | Professor Emile Pierre Van Ermengem identifies Clostridium botulinum as causative agent of botulism |
| 1895–1915 | Seven serotypes of toxins are recognized |
| 1928 | Dr Herman Sommer isolates most potent serotype: BoNT-A |
| 1946 | Carl Lamanna and James Duff develop concentration and crystallization techniques subsequently used by Dr Edward J. Schantz at Fort Detrick, Maryland, for possible biological weapon |
| 1972 | Dr Schantz takes his research to the University of Wisconsin, where he produces the large batch of BoNT-A that remained in clinical use until December 1997 |
Table 3.2 Timeline of therapeutic development and use
| Late 1960s–early 1970s | Dr Alan Scott begins animal experimentation with BoNT-A supplied by Dr Schantz |
| 1973 | Dr Scott publishes the first report of BoNT-A in primates |
| 1978 | FDA grants approval to begin testing small amounts of the toxin (Oculinum) in human volunteers |
| 1980 | Landmark paper demonstrating that BoNT-A corrects gaze misalignment in humans |
| 1988 | Allergan Inc. acquires rights to distribute Dr Scott’s Oculinum in the United States |
| 1989– | FDA approves BoNT-A for the non-surgical correction of strabismus, blepharospasm, hemifacial spasm, and Meige syndrome in adults Clinical use expands to include treatment of cervical dystonia and spasmodic torticollis Allergan purchases Dr Scott’s company and renames the toxin Botox® |
Serendipitous discovery
By the late 1980s, nearly 10 000 patients had received injections of BoNT type A (BoNT-A; then called ‘Oculinum’ and distributed to qualified injectors by Dr Alan Scott of the Smith Kettlewell Institute of Visual Sciences, San Francisco, CA) for the treatment of strabismus, benign essential blepharospasm, and hemifacial spasm (Smith Kettlewell 1990.) Many of these patients had received multiple injections with no evidence of antibody formation or systemic complications over 6 years of continued use. In Vancouver, British Columbia, ophthalmologist Dr Jean Carruthers noticed a remarkable and unexpected effect in the brow of a patient treated for blepharospasm: a noticeable reduction in the appearance of glabellar furrows, giving her a more serene, untroubled expression. Dr Carruthers discussed the observation with her dermatologist spouse, Dr Alastair Carruthers, who was attempting to soften the forehead wrinkles of his patients using soft-tissue-augmenting agents available in the eighties.
