A Look at How Botox Came to Be

The origin story of this ultra-versatile medical treatment.

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When it comes to aesthetic interventions, injection of Botox or botulinum toxin is the most common cosmetic procedure performed today. The American Society of Plastic Surgeons estimates that in 2014 nearly 7 million people received botulinum toxin injections.

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 (blepharospasm), neck contracture (cervical dystonia), migraines and overactive bladder.

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

What Is Botox?

Botox or botulinum toxin is produced by the bacterium Clostridium botulinum. In the wild, infection with Clostridium botulinum causes botulism, a rare but disabling paralytic illness.

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

After injection into the muscle, botulinum toxin suffuses the nerve terminal and binds thus preventing release of acetylcholine, a neurotransmitter. Without acetylcholine, muscle activity stops. This focal paralysis is what smoothes wrinkles and stops spasms.

In addition to messing with acetylcholine release, botulinum toxin also screws 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. 

Before injection with botulinum toxin, use of anticoagulants should be discontinued for two weeks to minimize bruising.

Pain at the injection site can be minimized with use of a small-gauge needle, application of a topical anesthetic or icing the area before injection. Furthermore, treatment with botulinum toxin should be started at a lower dose and gradually increased.

The effects of botulinum toxin wear off during time. Specifically after initial chemical denervation, the nerve ends sprout or regenerate and functionality is restored after 120 days.

There is no generic version of botulinum toxin, with several formulations on the market including Botox and Dysport. These formulations are not interchangeable and are dosed differently. These separate iterations of botulinum toxin vary by molecular weight, excipients, and complexing proteins.

The Origins of Botox

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 (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 licensed 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:

  • strabismus and blepharospasm in 1989
  • cervical dystonia in 2000
  • glabellar lines in 2002
  • axillary hyperhidrosis (excessive sweating) in 2004
  • chronic migraines and upper lip spasticity in 2010
  • urinary incontinence in 2011
  • 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 the annals of medicine, botulinum toxin is probably most significant 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.


Cochrane review titled "Botulinum toxin for facial wrinkles (Protocol)" by CP Camargo and co-authors published in 2014.  Accessed on 10/3/2015.

Article titled "Aesthetic Uses of the Botulinum Toxin" by A Dorizas and co-authors published in Dermatologic Clinics in 2014.  Accessed on 10/3/2015.

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