Botox. This powerful protein has become somewhat of a meme for people of a certain age wanting to look less than that age. Botox’s applications, however, go far beyond the cosmetic, as industry headlines in 2020 about Abbvie’s (North Chicago, IL) acquisition of Botox maker Allergan (Irvine, CA) reminds us. Contrary to the popular perception that Botox is solely for facial treatments, its applications span a multitude of medical conditions including hyperhidrosis, overactive bladder, and excessive drooling. Let’s explore the science of Botox and its many medical uses.

Botox is a neurotoxin—a substance that destroys nerve tissue. It’s produced by the bacterium Clostridium botulinum and causes botulism, a rare but sometimes deadly illness. Botulinum, (Botox’s formal name) interferes with key muscles in the body. This results in paralysis and even death. People contract food-borne botulism typically by eating home-canned food that has been prepared incorrectly. Botulism toxin is one of nature’s most lethal toxins. It’s twice as potent as the tetanus toxin and 100,000 times as potent as the poison gas sarin.

How in the world did such a deadly substance become a medicine? It all comes down to dose. The amount of toxin used for medical or cosmetic purposes is miniscule. It’s estimated that a baby-aspirin-sized amount of the powdered toxin is enough to provide the global supply of Botox for a year.

How does Botox paralyze muscles? Botox works by blocking acetylcholine. Motor neurons release this neurotransmitter to activate muscles. Putting the brakes on acetylcholine puts the brakes on our muscles. Unchecked, the toxin can kill by freezing the diaphragm muscles, leading to respiratory failure.

This paralyzing toxin can benefit human health in very small, localized doses. The FDA first approved the toxin in 1989 to treat strabismus, otherwise known as cross-eyes. Strabismus is caused by overactivity in one of the two muscles responsible for lateral eye movement. Relaxing the muscle results in normal eye alignment. Some “mature” strabismus patients who received Botox injections noticed a welcome side effect: fewer wrinkles between their eyes. By temporarily paralyzing the “frown” muscles, Botox made the unwanted furrow disappear. The FDA officially approved Botox for cosmetic use in 2002.

Since then, the FDA has approved many other indications: overactive bladder syndrome, chronic migraine, upper and lower limb spasticity, cervical dystonia, eyelid spasms, and excessive sweating.

Atrial fibrillation—an abnormal heart rhythm—can result from heart surgery. Researchers are finding that Botox may also have another vital role to play here. Preliminary studies suggest that injecting the neurotoxin into the nerve-rich fatty pads of tissue outside the heart reduces the rate of atrial fibrillation and related complications in cardiac patients. Presumably, the benefit comes from temporarily blocking nerve signals to the heart. Larger scale studies will determine whether this should become the standard treatment.

Botox is just one of many drugs developed for one condition only to yield unexpected second (or third, or fourth…) applications. Some of the best-known include:

• Lumigen (Allergan) was originally approved for glaucoma. Patients and physicians noticed that it also resulted in long, lush eyelash growth. A version of the drug for cosmetic purposes sells under the brand name Latisse.
• Proscar (Merck; Kenilworth, NJ ) was initially approved to treat enlarged prostrate, but came with the happy side effect of decreasing malepattern baldness. Propecia is the version marketed for baldness.
• And of course, Pfizer’s (New York, NY) Viagra was originally being developed to treat high blood pressure, an indication which proved unsuccessful. But, oh what a failure!

Poisonous animals also provide a seemingly dangerous source of lifesaving remedies. Again, the dose makes the difference, as do harvest methods! Examples include:

• Captopril, a high blood pressure medicine, is based on pit viper toxin. It was developed by Bristol-Myers Squibb (New York, NY) and approved by the FDA in 1984.
• Another gift from the pit viper is Defibrase, which can stop bleeding. It comes from a purified version of a protein found in the snake’s venom. It was developed by Pentapharm (Basel, Switzerland) and has been approved in Japan.
• Prialt, an analgesic for severe and chronic pain, comes from a toxin produced by the cone snail. Approved in 2004, it was developed by Elan Pharmaceuticals, now Jazz Pharmaceuticals (Dublin, Ireland).
• Integrilin, a powerful anti-clotting drug, derives from the venom of southeastern pygmy rattlesnakes. It was developed by Millennium Pharmaceuticals (Cambridge, MA) and approved in 1998.
• Byetta helps control blood glucose levels in type 2 diabetics and is a synthetic version of a protein obtained from Gila monster venom. It was developed by Amylin Pharmaceuticals (San Diego, CA) and approved in 2005.