Once Upon a Wrinkle

by Rachel Milligan · May 19, 2018

Image Credit: Marco M. via flickr.com

Botox. It’s become a household name in the last 15 years, with those of us who indulge in celebrity gossip always interested to know about the latest personality to have had some work. Some have maybe even taken it too far, with certain celebrities able to show about as much emotion as their waxworks in Madame Tussauds. But I’m sure the question many of you are asking is: what exactly is this so-called ‘wrinkle-eraser’ and how does it work? Well, allow me to – pardon the pun – fill you in.

The secret ingredient that people are using to banish their furrowed brows is actually one of the deadliest toxins known to man. Its name – the botulinum toxin. A substance so poisonous that just 450kg of it (about the weight of a piano) could wipe of the whole of humanity! With that in mind, you really have to question the person who thought it would be a perfectly good idea to inject people with the stuff!

The story begins back in the 19th century, when outbreaks of ‘sausage poisoning’ were rife in the streets of Germany. Many people were affected by this nasty illness, presenting with symptoms such as vomiting and diarrhoea; in extreme cases, this disease led to paralysis and even death. As it was unlikely that the illness was being caused by an army of killer sausages, scientists of the time began an investigation into what exactly was causing this fatal paralytic food poisoning.

One of these scientists was a man named Justinus Kerner, who took his investigations to extreme lengths by experimenting on himself. While some may call this dedication to his work, others may call it sheer lunacy. Kerner’s professor, who was thankfully one of the latter, managed to convince Kerner to stick to animal models instead. Success resulted from his studies however, as he discovered that the disease was in fact caused by a toxin that impaired both the somatic nervous system (responsible for voluntary muscle movements), and the autonomic nervous system which controls involuntary muscle movements, such as breathing and heartbeat. He also noted that this toxin did not have an effect on mental or sensory function, which led him to believe that this poison could somehow be of therapeutic use to humans, 150 years before it was actually proven to be true ¹.

Let us move on to 1895, by which time ‘sausage poisoning’ had been renamed botulism – a fancier sounding, Latin term for sausage. Emile Pierre Marie Van Ermengem was investigating another outbreak of the disease, this time caused by contaminated smoked ham. This was no match for the experienced professor, who became the first to grow the bacteria responsible for producing the toxin. He first named the bacterium Bacillus botulinus. However, this was short lived as, although the bacteria could produce spores, it could not be grown in the presence of oxygen. This was not typical of Bacillus species, as they rely on oxygen for their growth, and so the bacterium was placed in the Clostridium family with other spore-forming, anaerobic bacteria. Consequently, the bacterium was named Clostridium botulinum, while the neurotoxin was named botulinum (often shortened to BTX or BoNT).

This major breakthrough meant that it was now possible to culture the bacteria and carry out studies on its mode of action. In 1949 it was discovered that the BoNT works by blocking the signals sent from the brain to the muscles in the body. These signals are carried by messengers through neurons, which are like long telephone wires that the brain uses to communicate with the rest of the body. Once the messenger reaches its destination at the neuromuscular junction, it is transported by a tiny bubble across to the muscle, alerting it to the fact that it’s got a job to do. The messenger responsible for muscle contraction is called acetylcholine and it is this particular messenger that the BoNT blocks. The toxin breaks the ‘docking stations’ of the tiny acetylcholine-containing bubbles, meaning that the muscle is unaware that the brain is sending it information, as the ‘phone wires’ have been disrupted and communication has been blocked. This results in temporarily reduced muscle contractions, as the toxin wears off after a few months when new neurons grow and are able to overcome the effects of the toxin.

This led researchers to begin looking at therapeutic uses for the poison, and so, in 1973, an ophthalmologist named Alan Scott purified it and injected tiny amounts of it into monkeys with crossed-eyes to see if it could improve their condition. The study was a success and showed no side effects, paving the way for further therapeutic uses. The use of the purified toxin diluted in saline meant that it could still paralyse the muscles, but as it was injected into the body it was limited to migrating only 2 centimetres from the injection site, and so the risk of developing botulism was highly unlikely. By the end of the 1900s, the toxin had been approved for use in humans to treat various eye conditions and hemifacial spasms, to reduce excessive muscle contractions, and even to treat migraines and excessive sweating!

The cosmetic application of the toxin was accidentally discovered when ophthalmologists Jean and Alistair Carruthers noticed that patients getting treated for crossed eyes and twitching eyelids appeared to show diminished frown lines around the site of injection ². Their revolutionary suggestion to use this cosmetically was first viewed as a preposterous idea. However, after clinical trials proved this to be safe, the FDA (Food and Drug Administration) approved the toxin for cosmetic use in 2002. And so, along came the birth of Botox, leading to an epidemic of expressionless faces both in the celebrity world and amongst regular people who hope that it will prolong their youth.

The lethal dose of intravenously injected botulinum toxin is 150 nanograms, which is 15 million times less than the weight of a paperclip! However, the amount of the neurotoxin administered in therapeutic and cosmetic treatments is far less than this, and the dose also varies depending on the size of the target muscles. In larger muscles, such as the leg muscles, a total of 14.4 nanograms of the toxin is given, whereas for cosmetic purposes, as little as 1.4 nanograms is effective in ironing out those forehead creases. This procedure is not completely risk-free however, as the slip of the surgeon’s hand could lead to paralysis of the wrong muscles – not exactly ideal in the case of droopy eyelids. Procedures around the neck area are particularly risky since that’s where the muscles that help you breathe are located. Other side effects have been noted, such as difficulty swallowing and muscle weakness if the toxin manages to spread further than the site of injection ³.

While all of this doesn’t mean that saving up a Greggs sausage roll for a few weeks will provide a cheap, DIY alternative to sorting out your crow’s feet and forehead creases, it does really make you think about just how far this toxin has come in the last 150 years. It can not only be used to relieve the symptoms of muscle hyperactivity, but has become the world’s most popular type of cosmetic surgery, with over 6 million Botox procedures carried out each year. The botulinum toxin remains one of the deadliest poisons known to man, yet it can be manipulated to provide both therapeutic and cosmetic uses, which just goes to show that the botulinum toxin truly is a miracle poison. ⁴.

This article was specialist edited by Teodora Aldea and copy edited by Jessica Bownes.