Botox – Miracle drug or deadly bioweapon?

Botox – Miracle drug or deadly bioweapon?

Undoubtedly the most popular cosmetic drug currently on the market, Botox is a trademarked therapeutic widely used to reduce facial wrinkles, but is also used in the treatment of muscle hypersensitivity, migraines and even premature ejaculation. In the USA alone, there were 7.23 million documented Botox procedures in 2017.

However, what is perhaps less known about Botox is that it is actually an extremely potent neurotoxin. So what is it that makes Botox both an effective treatment for muscular disorders, and a terrifying bioweapon at the same time?


What is Botox, and how does it work?

Botox is actually shorthand for Botulinum toxin, a protein produced by the bacterium Clostridium Botulinum under anaerobic conditions. This protein causes botulism, a disease characterised by symptoms of weakness, fatigue and vomiting, followed by blurry vision and difficulty in swallowing and speaking. In extreme cases, paralysis followed by respiratory failure and death can occur.

The 3D structure of botulinum toxin, with the molecular formula of C6760H10447N1743O2010S32

This is because botulinum toxin is a neurotoxin which prevents the transport of signals between nerves, such that muscles in the respiratory system (such as the diaphragm, intercoastal muscles) cannot contract, preventing gas exchange which is essential for respiration, and by extension, life.

Let’s get into more detail:  

While the mechanism of how botulinum toxin works is surprisingly simple, it is important to first understand how signals are transmitted between neurones:

The space in-between two neurones is called a synapse or synaptic cleft. In particular, we are concerned with the neuromuscular junction, which is between a motor neurone and a muscle.

When an electrical impulse arrives at the neuromuscular junction, it causes calcium ions to enter the synaptic bulb of the neurone, which bind to vesicles containing a neurotransmitter called acetylcholine. This then causes the vesicles to attach to SNARE proteins inside the cell surface membrane of the synaptic bulb, which allows the vesicle and cell membrane to fuse, releasing the neurotransmitter to diffuse across the synapse. Once the acetylcholine reaches the receptors on the muscle cells, the signal has successfully been transferred across the synapse, and muscle contraction can take place. 

A diagram of the neuromuscular junciton, during the transfer of an electrical signal

Botulinum toxin is actually a protease, or enzyme which breaks down proteins. When released, it will cleave and destroy the SNARE proteins which mediate the process of exocytosis (the binding of vesicle with the cell membrane to release its contents), preventing any acetylcholine from being released. This has a long lasting effect of months, and during that time the muscle is said to be in a state of flaccid paralysis, where it is unable to contract naturally.


A diagram showing SNAP/SNARE proteins during the process of exocytosis

tl;dr: Botulinum toxin is a protein which prevents the release of neurotransmitter between neurones and muscles, so muscles are unable to contract when a signal is directed towards it. This leads to a state of paralysis for several months.


Botulinum toxin as a bioweapon

Let’s say, for the sake of argument, that you are a Gotham city-esque villain with a strong desire to poison the city’s water supply. My personal toxin of choice (hypothetically) would be botulinum toxin. Why? Because it is both lethal in microscopic doses and easy to acquire. Let’s take a look at the stats:

Assuming that the toxin is inhaled, and assuming the global average weight for men and women separately, here’s the lethal dose of botulinum toxin (PMID 11209178):

-        Men: 713ng, or 7.13 x10-7 g, or 0.000000713g

-        Women: 656 ng, or 6.56x10-7g, or 0.000000656g

What really puts this frightening statistic into scale, is that it takes only about 5.5 kilograms of pure botulinum toxin to kill all 8 billion people on the planet. It is by far the most toxic biological substance known to science.

Botulinum toxin is also more common than you would think. The leading cause of botulism is from improper food treatment, especially in canned preservatives. It can also arise from fermenting food without enough acidity or salt, usually by the amateur home cook. It is not unreasonable, then, to imagine that one can simply extract the bacteria that are growing and culture them in anaerobic conditions to produce large amounts of toxin. Just a thought.

Before I proceed, I would like to clarify to any worried readers that naturally occuring botulism is actually not very deadly, with an untreated mortality rate of about 5~10%. The body naturally prevents any Clostridium botulinum from growing in the gut (unless you are an infant), and it is very treatable with available antitoxins (which are just antibodies). As long as you seek medical attention when you start developing the symptoms mentioned above, then it is 100% treatable (manufactured botulinum toxin, however, is a different story).


Botulinum toxin as a treatment

However, there are two sides to the same coin: Botulinum toxin is also a drug with high utility and flexibility, as the ability to paralyse specific muscles is very useful in a medical context. Interestingly, while it is the most toxic substance we currently know of, it was also the first bacterial toxin licensed by the USFDA as a drug for human treatment, in 1989.

As we already know, Botox is a drug used for mainly cosmetic purposes. By paralysing facial muscles, it removes creasing and wrinkles from the face. It is also a treatment for drooping/spasming eyelids for the same reason. Botox is also used in a variety of treatments for similar neurological disorders, including chronic migraines, skeletal muscular spasms after CNS injury, and facial spasms and cramps.

My personal favourite applications of Botox include (not in this order) treating chronic anal fissures, erectile dysfunction and debarking dogs (not so sure about this last one, but take a look if interested: PMID: 21149997,  PMID: 9826986).

In conclusion, Botulinum toxin is a versatile substance which can be used for both beneficial and maleficial purposes. Whether you wish to commit a genocide, treat muscular and neurological diseases, silence the neighbours dog or simply remove some wrinkles from your aging face, Botox is the way. Even today, scientists are still finding new applications for this drug given its flexibility and utility. If there is a lesson to be learned here, it would be this: if you keep your mind open, even the most toxic of drugs can be made to do good.