Thou art watching, and thou only, Above the earth’s snow tomb; Thus lovely, and thus lonely, I bless thee for thy bloom. ~ Letitia Elizabeth Landon, “The Snowdrop”
Snowdrops growing on a forest ground.
Sometimes it’s the smallest of voices, the tiniest of things, that make the greatest changes to our lives, the biggest impact on the world. These are things that give us hope at times of despair.
This was what came to mind when I realised how truly impressive these flowers are. I’m talking about Snowdrops – or Galanthus – a genus of about 20 species of dainty bulbous, bell-shaped white flowers.
Whether you’ve seen or heard about them or not, I’m sure you’ll be amazed by at least one of their attributes, even if it’s just the simple beauty of their common name.
There’s something in here for everyone, especially if you’re into Greek mythology, pharmacology, medical sciences, history, arts and literature, or all of them.
So let’s go back to 8th century B.C, when Homer wrote the famous “Odyssey”, and look at where snowdrop made its subtle appearance.
Moly – The antidote to Circe’s Poison
It all began with Odysseus’ expedition to the Phaeacians (books 9-12 of the 20 in Odyssey). He and his men arrived on their ship, and a quick scout from a high point revealed that there was a fire on the island. Odysseus separated his men into two groups, one of which was placed under the command of his brother-in-law, Eurylochus. They drew lots and decided the Eurylochus’ team would investigate the fire on the island.
Unfortunately, that was how Eurylochus’ team found Circe’s house and got drawn inside by a sweet singing voice. It all turned out to be a trap – the men were poisoned by Circe’s hallucinogenic drugs and enchanted by her spells until they forgot their purpose of their exploration and refused to return to Odysseus. Odysseus eventually learned of this situation from Eurylochus, who was vigilant enough to see through Circe’s tricks and had returned alone to explain what had happened.
Naturally, Odysseus went to save his men. However, he was stopped by Hermes at the front of Circe’s home, who insisted Odysseus would fail his mission and end up like the rest of his men if he went in without help. So Hermes offered Odysseus a “good drug”, which would – and did – protect Odysseus against the effects of Circe’s “bad drugs” [1,2].
Enchanted by Circe. Cup (skyphos), 425-375 BC. The drawing on this Greek skyphos cup depicts Circe offering Odysseus a poisoned drug. However, Odysseus is protected by an antidote – moly – given to him by Hermes (Source | License).
This mysterious drug was described as “black at the root, but with a milky flower. The gods call it moly. It is hard for mortal men to dig up,” but not for the gods” [2].
Moly, the magical antidote, was eventually identified as snowdrop. As with most things, science was what helped people figure out its identity.
Dioscorides, a Greek physician and the “father of pharmacognosy”, proposed that Circe’s drugs were derived from Datura stramonium, or jimsonweed (also called devil’s trumpet, thorn apple, or devil’s snare – fitting names I would say) to poison her victims. Jimsonweed contain tropane alkaloids like atropine and hyoscyamine, which cause memory loss and delirium [3], in agreement with the hallucinogenic effects suffered by Eurylochus’ men.
Dioscorides realised that Galanthus nivalis, or the common snowdrop, was able to counter the effects of jimsonweed, and that was how the moly’s identity came to light.
Pharmacology explains it all: the tropane alkaloids were in fact anti-cholinergics, substances that repress the action of a neurotransmitter called acetylcholine (ACh). The fact that moly was able to counter the anti-cholinergic effects suggest that it could contain cholinergic substances, which can increase the amount or activity of ACh [4].
Understanding this was how galantamine – named after the flower from which it was extracted – came to be a revolutionary treatment in one of the most common form of dementia in the UK.
Galantamine in Alzheimer’s Disease
This following section is for the pharmocology enthusiasts out there (like me) who wants to know how drugs work. Indeed, it is pretty fascinating that a chemical from a seemingly harmless plant is able to change how the mind functions.
To begin, it is necessary to explain what Alzheimer’s is at the physiological level. Alzheimer’s Disease (AD) is a type of dementia, characterised by memory loss due to the loss of cholinergic neurones — neurones stimulated by acetylcholine (ACh) [5]. ACh action affects memory and learning, among many other important, everyday functions. Reduced cholinergic transmission in AD therefore causes the cognitive disabilities we see in patients, from learning difficulty to hallucinations and delirium [6].
One way to treat AD is to increase the amount of ACh at cholinergic synapses (the gaps between two neurones), and this is exactly galantamine, extracted from snowdrops, does.
Galantamine achieves this using two mechanisms:
As a competitive inhibitor of acetylcholinesterase (AChE)
AChE breaks down ACh in synapses to terminate a nerve stimuli after neurones have been fired for a period of time, and is usually very important in regulating responses – so your muscles don’t contract and stay contracted for too long, for example.
However, AChE activity can actually worsen the symptoms of AD by further reducing the amount of cholinergic transmission.
As a competitive inhibitor, galantamine binds to the active site of AChE and prevents it from degrading the already scarce ACh in the synapses of AD patients. This increases the amount of ACh circulating around the nerve terminals and thus encourage cholinergic transmission [5].
As an allosteric modulator of nicotinic acetylcholine receptors (nAChR)
nAChRs are ion channels found on the nerve terminals, often on the post-synaptic membrane of neuromuscular junctions.
They respond to ACh by opening the ion channels and allowing influx of sodium ions from the synapse into the post-synaptic neurone, which passes on the action potential and transmits the signal to the next neurone or the target organ.
nAChRs are made up of smaller subunits, and ACh binds to an α subunit to exert its effects. Galantamine also binds to the α subunit of the receptor, but on a different site — an allosteric one — to change the receptor function.
When galantamine and ACh are both bound to nAChRs at the same time, they work synergistically to increase the receptor’s sensitivity and responsiveness to ACh, thus strengthening cholinergic transmission [5].
Galantamine mechanism of action. Galantamine treats Alzheimer's Disease using its dual mechanism: as a competitive inhibitor of acetylcholinesterase (AChE), and as an allosteric modulator of nicotinic acetylcholine receptors (nAChRs) (Lilienfield, 2002).
The second mechanism listed makes galantamine especially unique — it is the only marketed drug treatment for AD that has a function as an allosteric modulator [5].
The Snowdrop fact sheet
All the mythology and science might be making your head spin, so this final section will end off the article on a light-hearted tone. If the relationships between snowdrops and mythology/pharmacology aren’t quite your cup of tea, here are some fun facts about the flower to share with your friends:
Snowdrops was a nickname for the military police of the US army, termed by British People during the Second World War. This is because the MP wore white helmets, gloves, gaiters, and a brown belt over their olive uniform.
Snowdrops are used in many arts and literature pieces, including the poem by Letitia Elizabeth Landon, “The Snowdrop”, which was featured in the beginning of this article. You can read the full piece here.
Tchaikovsky has a series of 12 piano pieces (”The Seasons”) named after each month of the year with a second name representing that month. The April piece was subtitled “Snow Drop.”
A Korean drama called “Snowdrop” was aired from December 2021 to January 2022, starring famous celebrities like actor Jung Hae In and singer Jisoo from famous K-Pop girl group BlackPink. (I personally have not seen the drama so I cannot comment on the relationship between the drama and the flower.)
Snowdrop is used as an alternative name for “Snow White” in the German version of “Snow White and the Seven Dwarfs”.
In the language of flowers, snowdrops symbolise hope as most species bloom during winter (Jan/Feb), signifying the arrival of spring.
As you can see, snowdrops have made their appearance in Greek mythology, expressed their beauty in art and literature, and have even persisted through the mutable popular culture.
So let’s continue looking for their traces and listen to what these small flowers have to tell us.
References:
Antigone. Circe, Odysseus and the Disclosure of Hermes [Internet]. Antigone. 2023 [cited 2024 Jan 24]. Available from: https://antigonejournal.com/2023/11/circe-odysseus-hermes
Homer. Odyssey, Book X. 1889.
Rojas-Sandoval J. Datura stramonium (jimsonweed). CABI. 2022, Jan, 7
Plaitakis, Andreas; Duvoisin, Roger C.. Homer's Moly Identified as Galanthus nivalis L.: Physiologic Antidote to Stramonium Poisoning. Clinical Neuropharmacology 6(1):p 1-6, March 1983.
Lilienfeld S. Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer’s disease. CNS Drug Rev. 2002, Jun;8(2):159–76.
Alzheimer’s Disease [Internet]. NHS; 2021 [cited 2024 Jan 25]. Available from: https://www.nhs.uk/conditions/alzheimers-disease/symptoms/