Hello everyone and welcome to this week's blog post. This week's article is the first in a two-part series about poisons. In this article, I will be discussing what poisons are, before explaining how ricin and botulinum toxin work and how they can be treated. Next week, I will be discussing three other poisons, as well as exploring the mechanisms behind antidotes.
Introduction
Poisons are substances that can cause severe harm to an organism by damaging tissues and/or disrupting chemical reactions and mechanisms. To cause damage, they need to enter the organism. This most commonly occurs when substances are ingested, injected into the bloodstream, inhaled, or absorbed through the skin.
Technically, any substance (including water) can be poisonous if taken in high enough quantities. For example, water has an LD50 of 90g per 1kg. LD50 is one of the most commonly used figures when comparing the toxicity of different substances. This figure gives the amount of substance required to kill 50% of the animals tested on. Consequently, a person weighing 75kg would need to drink roughly 6-7 litres of water in one go before they died (this is only an average though, and would depend on the person's age and medical fitness).
Poisons are found in many places in the natural world. For example, some are used by organisms to break down food and nutrients. Meanwhile, others are used by organisms in conjunction with bright colours as a deterrent, to try and discourage predators to eat it. This type of behaviour is called aposematism. For example, the poison dart frogs in Central and South America have brightly coloured bodies that advertise their toxicity. Whilst scientists are unsure about how these frogs get their toxicity, it is thought that assimilate the plant poisons carried by their prey (e.g. ants).
Toxins have been used by humans throughout our history for many purposes, including for use in pesticides, preservatives, anti-venoms and medicines. In addition, poisons can also be used as weapons. For instance, hunters would coat arrow-tips with natural poisons (such as poisons from poison dart frogs). This made hunting animals much easier. Indeed, some tribes still use this technique today.
Ricin
Ricin is an incredibly deadly poison, which is found in the seeds of castor oil plants. This poison has an LD50 of around 22 micrograms per kilogram of bodyweight if inhaled (or 1 milligram per kilogram if ingested). According to the Mayo Clinic, symptoms of ricin poisoning include having a fever, chest tightness and other respiratory problems. In addition, if ingested, ricin can also cause organ damage, bleeding in the intestines and eventually death.
Ricin is deadly as it binds to carbohydrates found on the cell surface membrane. This allows the molecule to enter the cell and interferes with the ribosomes inside the cell. Since these ribosomes are responsible for converting mRNA into proteins, the cells affected by the poison are no longer able to make proteins. Without proteins, these cells stop functioning and result in the symptoms of ricin poisoning.
Unfortunately, there is no antidote for ricin, so it is very important that people reduce their exposure to ricin and remove contaminated clothes as quickly as possible. Treatment can then be provided to treat the symptoms of ricin poisoning and limit the effects of the poison. For example, patients can be ventilated to help them breathe. In addition, they can also be given activated charcoal if the ricin was ingested, as it binds to toxins in the stomach.
Whilst ricin is incredibly poisonous, it may have some uses in modern medicine. According to a review paper published in Tumor Biology, ricin may act as a chemotherapeutic agent for cancer treatment. This is because ricin is able to inhibit protein synthesis and cause cells to undergo apoptosis (programmed cell death). Consequently, if nanoparticles are used to deliver the ricin to the cancer cells, the ricin may be able to destroy these cells without harming the rest of the body.
Botulinum
Botulinum toxin, which is also known as botox, is a toxin produced by the bacteria Clostridium botulinum. This bacteria produces botulinum toxins in low-oxygen conditions. The botulinum it produces can be split into 7 different neurotoxins, which are structurally similar but have different antigens and different effects on the body. These neurotoxins are types A, B, C1/C2, D, E, F and G). According to Medscape, types A, B and E are the main types which commonly cause disease in humans. Meanwhile, types C, D and E cause disease in other mammals, fish and birds.
One of the reasons that botulinum toxins are dangerous is that the spores produced by the bacteria are heat-resistant and thus stay in the environment for a long time. Under anaerobic conditions, they can then grow and produce the toxins.
There are many ways that the toxin can enter the human body and cause disease. For example, the botulinum toxin can be ingested - there have been several cases where the toxin has been found on fish, meat products and low-acid preserved vegetables (as the bacterium can't grow in acidic conditions).
In addition, infant botulism can also occur. This is when infants ingest the bacterium spores, causing the spores to colonise the gut and release these toxins over time. This type of infection is called infant botulism as it mostly occurs in infants under the age of 1 year old since the body's immune system and natural defences are not sufficiently developed. Nevertheless, it is still possible for adults to contract this pathogen. This occurs during 'wound botulism' - when the spores enter the blood through a wound on the skin.
According to the World Health Organisation, this toxin can also be inhaled. Whilst this does not occur naturally, it is possible for this toxin to be turned into an aerosolised bioweapon. Furthermore, this toxin can also theoretically be transmitted through the water, though common water-treatment processes would destroy it, so this risk is considered low.
The botulinum toxin is a neurotoxin, meaning that it acts on the nerves in the body and prevents the body from using the nervous system to coordinate actions. The toxin first binds to the axon terminals of neurones which use acetylcholine as their neurotransmitter, allowing them to be absorbed into the cell. After entering the cell, the toxin splits proteins inside the cell into two pieces. This has several effects, including preventing vesicles full of acetylcholine from binding to the axon endings, thus stopping the nerves from working.
Botulinum is a very deadly toxin - it has an LD50 of around 1-3 nanograms per kilogram. According to the NHS, the symptoms of botulin infection can take as long as several days to develop. Initial symptoms of infection include feeling sick, vomiting, diarrhoea, and stomach cramps. When the disease develops, paralysis starts to spread across the body. This results in drooping eyelids, double vision, muscle weakness, slurred speech and difficulty swallowing. If the muscles involved with breathing get paralysed, then breathing difficulties and death can also occur.
Botulism can be treated by using antitoxins or antidotes to neutralise the toxin and prevent it from causing more harm to the body. Additionally, the symptoms of botulism can also be treated to allow the body to naturally fight the toxin. For example, patients who have trouble breathing can be ventilated.
Botulinum toxin can also be used as part of cosmetic procedures. The botulinum used for this purpose is often known by its trade name - 'Botox'. This works as the toxin temporarily blocks signals from travelling through the nerves to these muscles. Consequently, the injected muscles temporarily relax, causing lines and wrinkles to be smoothed out.
I hope you have enjoyed this week's article. Make sure to subscribe to the mailing list below so that you get notified of next week's article, which will be discussing how tetrodotoxin, batrachotoxin and cyanide work, as well as exploring the mechanism behind antidotes.
Sources:
Tyagi, N., Tyagi, M., Pachauri, M., & Ghosh, P. C. (2015). Potential therapeutic applications of plant toxin-ricin in cancer: challenges and advances. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine, 36(11), 8239–8246. https://doi.org/10.1007/s13277-015-4028-4
Dressler, D., Saberi, F. A., & Barbosa, E. R. (2005). Botulinum toxin: mechanisms of action. Arquivos de neuro-psiquiatria, 63(1), 180–185. https://doi.org/10.1590/s0004-282x2005000100035
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