The Remarkable History of Botox

When it comes to aesthetic interventions, injection of botulinum toxin is the most common cosmetic procedure performed today. The American Society of Plastic Surgeons estimates that in 2018 more than seven million people received botulinum toxin injections. To put that number into better perspective, more people receive botulinum toxin injections in a year than live in Arizona.

Woman getting an injection in her cheek
Robert Daly / Getty Images

Most people associate botulinum toxin injections with the treatment of wrinkles; however, this remarkable agent is extremely versatile and used for many other conditions, including spasticity, eye twitch (i.e., blepharospasm), neck contracture (i.e., cervical dystonia), migraines, and overactive bladder. Botox is also used for the treatment of severe underarm sweating (i.e., hyperhidrosis).

The story of how we came to inject this microbial toxin into our bodies to treat wrinkles is both fascinating and serendipitous.

What Is Botulinum Toxin?

Botulinum toxin is produced by the bacterium Clostridium botulinum. In the wild, infection with Clostridium botulinum causes botulism, a rare but disabling paralytic illness. Botulism starts by paralyzing the muscles of the face, mouth, and throat before spreading to the rest of the body. When botulism paralyzes the muscles used in breathing, death can ensue. Of note, in May 2017, there was a botulism outbreak in California traced back to nacho cheese sauce sold at a gas station. As a result, 10 people were hospitalized and one person died.

Although Clostridium botulinum comes in several strains—eight serotypes A, B, C1, C2, D, E, F, and G—only serotypes A and B are used to create clinical preparations.

How It Works

After injection into the muscle, botulinum toxin suffuses the nerve terminal and binds thus preventing the release of acetylcholine, a neurotransmitter. Without acetylcholine, muscle activity stops. This focal, or site-specific, paralysis is what smoothes wrinkles and stops spasms. In other words, botulinum toxin works by "paralyzing" the wrinkles away.

In addition to interfering with acetylcholine release, botulinum toxin also interferes with the release of pain and inflammatory mediators including substance P and glutamine, which explains why botulinum toxin is used to treat migraine headaches.

Adverse effects after treatment with botulinum toxin include bruising, swelling, headaches, discomfort as well as muscle weakness which may affect muscles surrounding the muscle that was injected. Pain at the injection site can be minimized with the use of a small-gauge needle, application of a topical anesthetic or icing the area before injection.

The effects of botulinum toxin wear off during time. Specifically, after initial chemical de-nervation, the nerve ends sprout or regenerate and functionality is restored after after altering the nerve ending, Botulinum toxin works for about four to six months before the nerves regenerate. In a few individuals, the standard dose will not produce the desired result. In such cases a second dose may be administered.

Botulinum toxin type A is now manufactured by 5 separate pharmaceutical companies with the trade names Botox Cosmetic, Daxxify, Dysport, Xeomin, and Jeuveau. While they each have minor differences, the active ingredient of all is botulinum toxin, and they all work essentially the same.

The Origins of Botulinum Toxin

Clostridium botulinum was first discovered by a Belgian scientist named Emile Pierre van Ermengem following a botulism outbreak in Belgium. By the 1920s, scientists at the University of California, San Francisco, first tried to isolate the botulinum toxin. However, it took 20 years before the botulinum toxin was finally isolated in crystalline form by Dr. Edward Schantz.

In the 1970s, scientists started using botulinum toxin to treat strabismus (i.e., crossed eyes). While testing this treatment on monkeys, researchers noticed that botulinum toxin reduced wrinkles in the glabella. The glabella is the skin between the eyebrows and above the nose.

After botulinum toxin proved successful in the treatment of strabismus, Allergan was the first company to license the treatment and branded it Botox. Subsequently, Botox received FDA approval for a variety of medical and cosmetic uses.

Here are the dates of various FDA approvals for botulinum toxin:

  1. Strabismus and blepharospasm in 1989
  2. Cervical dystonia in 2000
  3. Glabellar lines in 2002
  4. Axillary hyperhidrosis (excessive sweating) in 2004
  5. Chronic migraines and upper lip spasticity in 2010
  6. Urinary incontinence in 2011
  7. Crow's feet (lateral canthal lines) in 2013

Please note that although physicians use botulinum toxin to treat many types of facial wrinkles, much of this treatment is off label. In other words, your physician uses clinical judgment to treat facial wrinkles with Botox.

In the annals of medicine, botulinum toxin is probably most notable because it was the first microbial injection used to treat disease. The injection of bacterial products into the human body represents a new invention. With each passing year, researchers develop more formulations of this versatile agent and find more uses for it.

A Word From Verywell

Botulinum is a versatile agent commonly used to treat many types of wrinkles. Overall, it is relatively safe, with few adverse effects. If you are interested in receiving botulinum toxin treatments, please speak with your dermatologist.

14 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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Additional Reading
  • Camargo, CP, et al. Botulinum toxin for facial wrinkles (Protocol). Cochrane Library.

  • Dorizas, A, Krueger, N, Sadick, NS. Aesthetic Uses of the Botulinum Toxin. Dermatologic Clinics. 2014; 32(1):23-36.

By Naveed Saleh, MD, MS
Naveed Saleh, MD, MS, is a medical writer and editor covering new treatments and trending health news.