Bluebell: Hyacinthoides non-scripta

[This post features my original artwork and botanical sketches]

I truly believe that revising for my upcoming exams and developing my understanding of the sciences is an enjoyable process, but when gentle dawn sunlight illuminates the vibrant azure bundles of flowers peppered throughout our garden, it takes the strength of every fibre in my being to not abandon my textbooks and immerse myself in the carpet of wild bluebells.

In two months, I’ll have sat all my AS exams and will finally be free to laze around in the grass with my cat and lie among the sea of indigo petals. Until then, I look to the shimmering haze of the bluebells as an oasis just fingertips away.

Recently, I rewarded my revision efforts by pressing an inflorescence and uncovering the chemistry behind their beautiful blue pigment*. The rich colour of the petals is not caused by a single true blue pigment but rather by the red pigment anthocyanin. The basic structure of the anthocyanin delphinidin is modified with pH shifts and prosthtic groups.

Delphinidin is pH sensitive and turns red in acidic environments. A high pH must be maintained to ensure the molecular pigment is blue. Delphinidin is also malonated; two glucosyl groups, a malonyl group, and a coumaryl group are bonded to the pigment structure. 

 

 

 

 

 

The resulting compound, malonylawobanin, is responsible for the brilliant deep blue petals that don’t even fade after weeks of pressing. 

I also consulted my copy of The Complete Herbal out of interest in the medicinal properties of this plant. Nicholas Culpeper was surprisingly brief in his writings of bluebells; he only refers to its somewhat styptic (blood clotting) qualities. From further research, I learnt that the bluebell’s intensely toxic nature has, understandably, limited its potential for therapeutic applications.

One of the major toxic compounds present in bluebells are polyhydroxylated pyrrolidines (such as nectrisine) which are found in the viscous sap that seeps out of the plant’s nodding stems. These compounds are analogues of sugar but are actually potent glucosidase inhibitors. Due to its many -OH groups, the mammalian body mistakes nectrisine as a sugar and processes it as such – inadvertantly allowing the molecule to interfere with respiration.

In addition to this, polyhydroxylated pyrrolizidines, which have a similar chemical action to nectrisine, are toxic alkaloids that have been proven to poison livestock that have the misfortune of ingesting bluebells. Despite this, these compounds are now being considered for use in cancer therapeutics.

Most fascinatingly, bluebells contain a type of cardiac glycoside, Scillaren A, which can rapidly increase the output force of the heart. Heart cells, myocytes, contain protein pumps embedded in their cell membranes which actively transport sodium ions out of the cell to create an essential electrochemical gradient. In the heart, there is also a sodium – calcium ion exchanger which maintains the ion homeostasis. 

Cardiac glycosides, such as Scillaren A found in bluebells, inhibit the movement of sodium ions out of the cell by effectively disabling the ion pumps. This increases the concentration of sodium ions inside the myocytes which, in turn, increases the calcium ion concentration as sodium ions inside the cell are exchanged for calcium ions.

In myocytes, the accumulation of calcium increases the power with which the cells can contract (contractility) – increasing cardiac muscle contraction which can be crucial in controlling the heart rate in cases of arrhythmia and even chemically restarting the heart in atrial fibrillation.

The cardiac action of Scillaren A is stronger than that of the commonly used digoxin, which is derived from foxglove, and is ideal for situations in which digoxin alone is insufficient or the patient has a digitalis intolerance. Additionally, if an improper dosage is administered, Scillaren A is poisonous but, unlike many other cardiac glucosides, is non-lethal as it is poorly absorbed into the gut. The compound also has a very high therapeutic index as it is rapidly eliminated from the body. All of these qualities make bluebells a fundamentally desirable pharmaceutical source, however, since native bluebells are an endangered and protected species, bluebells cannot be harvested to produce medication.

Conservation efforts are essential to protect and preserve this fragile, flowering species so that we may be able to enjoy their magnificent appearance and benefit from their therapeutic value in the coming decades.

 

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* White bluebells which lack pigmentation also exist albeit they are somewhat rare with only 1 in every 1000 native bluebells being white. Below is a pressed white bluebell I came across in Margate. 

Dandelion: Taraxacum Officinale

[This posts features my original botanical sketches]

For me, the most marvellous manifestations of spring are the bright dandelions emerging from previously barren, frost-glazed soil – bringing promises of brighter days to come.  The humble dandelion is so often maligned as a weed, however these perennial plants have a rich therapeutic history.

Nearly half a millennium ago, Nicolas Culpeper, a prominent herbalist of the early 1600s, noted that the dandelion has “an opening and cleansing quality” and remarked upon its efficacy at treating liver ailments (including cirrhosis) as well as diseases of the spleen and gall-bladder. Many of Culpeper’s contemporaries, and indeed modern herbalists, also acknowledge the powerful diuretic properties of dandelion leaves and root.

Dandelions have even proven valuable in cutting-edge pharmaceuticals. Researchers from the Department of Chemistry and Biochemistry at the University of Windsor, Canada,  have found that dandelion root extract can efficiently kill certain types of aggressive leukaemia cells. This extract can induce apoptosis (programmed cell death) and autophagy (wherein the cancer cell breaks down its own organelles), and even disrupt mitochondrial membranes. The lack of toxins and alkaloids in the plant, combined with the extract’s selectivity for leukaemia cells, makes the dandelion a particularly promising candidate for safe chemotherapy applications.

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Ovadje, P., Hamm, C., & Pandey, S. (2012). Efficient induction of extrinsic cell death by dandelion root extract in human chronic myelomonocytic leukemia (CMML) cells. PloS one, 7(2), e30604. doi:10.1371/journal.pone.0030604

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281857/

 

Toxicology Thursday: Cyanide

Cyanide, a deadly compound found in bitter almonds and apple seeds, consists of simply two atoms (Carbon and Nitrogen) bonded together as a unit. Cyanide is typically found in ionic compounds where it is bonded to one other positive ion (a cation); hydrogen cyanide and potassium cyanide are notorious examples.

The toxicity of cyanide depends on how easily the bond between the cyanide unit and the cation can be broken. For instance, in hydrogen cyanide, the bond between the H⁺ and the cyanide unit are easily broken so hydrogen cyanide is extremely toxic.

When cyanide enters the bloodstream, it attaches to the iron in haemoglobin – displacing oxygen. Once bonded to haemoglobin, cyanide can travel rapidly around the body and reach the mitochondria of the cells. Within the mitochondria, cyanide can bind irreversibly to cytochrome c oxidase (an important respiration enzyme) – preventing energy from being released into the cell and, eventually, killing the cell.

Rendering of Deer Mandible

 

A close-up sketch of the porous and undulating bone formations of the deer mandible that I found and examined a few years back – white pencil on black cartridge paper.

 

Toxicology Thursday: Opiates

Opium refers to the crude extract obtained from poppy plants. Opium itself is fairly easy to obtain directly from poppies but its effects on the body are rather mild in contrast to other modified forms of opium. Opium has been modified into several, more potent drugs known as opiates; most notably, these are morphine, codeine, and heroin.

Morphine was the first developed opiate; it is named after Morpheus (the Greek god of dreams) for it’s ability to put the user to sleep or even in a coma.

Codeine is the second most abundant alkaloid found in opium. To work in the body, enzymes must first convert codeine into morphine- codeine therefore is slower-acting and much less addictive.

Heroin (also known as diamorphine) is a modified form of morphine with two acetyl groups. The acetyl groups increase the compound’s solubility in fats meaning it can pass through the blood-brain barrier very easily, allowing it to interact directly with the opioid receptors in the brain- making it far more potent and addictive.

The greatest medical benefit  of opiates is that they provide pain-relief. However, there is a darker side to the relaxed state such drugs can put you in; in the case of an overdose, the sedation deepens rapidly into a coma and the respiration rate drops substantially since opiates reduce the sensitivity of the respirator centre. Eventually, the respiratory failure leads to death.

Toxicology Thursday: Digitalis

Digitalis is a very effective poison given that it is readily available and lethal in very small quantities. But before you start plotting the demise of your enemies, it is worth noting that digitalis is also detectable in very small quantities.

Digitalis refers to compounds extracted from foxgloves which have specific and dramatic effects on the heart . Digitoxin is one such compound ; it has a serious effect on the heart because of its ability to dampen the electrical signals that coordinate the contractions of the cardiac muscles. In low doses, this causes arrhythmia (an irregular heart beat). However, in higher doses, digitoxin can completely block electrical signalling – effectively paralysing the heart.

Interestingly enough, atropine (a different toxin) can be given to stimulate the heart and work as an antidote to digitoxin poisoning or overdose.

Toxicology Thursday: Eserine

The Calabar bean is a natural sources of poison with a rich cultural history.

In Nigeria, in the early 19th century, there was a practice of feeding a paste of these poisonous beans to people accused of witchcraft, murder, or rape. If the person on trial died from poisoning, they were guilty and, if they survived, they were innocent.

Contrary to popular belief, there may be more logic behind this judicial system than initially meets the eye; guilty defendants would be more cautious or fearful about being exposed and so might be inclined to swallow the paste more slowly than an innocent. A slow administration of the poison allows for a longer exposure time increasing the absorption of the poison and, hence, worsening its effects. If this notion was true in every case, in general, innocent defendants would become quite ill but guilty defendants would most likely die.

The active agent of Calabar beans is physostigimine (also known as eserine); this toxin also disrupts the parasympathetic nervous system but in a different manner to atropine.

Acetylcholine (an important neurotransmitter) must be broken down after it performs its task- otherwise, the neurotransmitter would keep activating receptors and produce unwanted effects in the body. Eserine inhibits the enzyme that breaks down acetylcholine – producing opposite (yet equally extreme) effects to atropine poisoning. Whilst atropine dilates the pupils, eserine constricts them. Similarly, whilst atropine causes heart palpitations ands a rapid pulse, eserine poisoning results in heart paralysis.

Spider Crab

white pencil and chalk on black cartridge paper

Nancy Rothwell Award 2018: Shortlisted

 

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Driven by my deep-rooted admiration of the orca, a beautifully designed cetacean, I spent the late summer days sketching for hours – trying to capture the fascinating form of the toothed whale. Whilst I was working on this drawing, I learnt about the fascinating science behind their adaptions for attack (such as the immensely powerful hypaxial muscles that allow it to wield its tail to paralyse prey and the streamlined body that enhances its hydrodynamic movement) and reflected this in my art.

I finally completed this intricate exploded view of the external anatomy, muscles, and skeleton in September and immediately entered it into the Nancy Rothwell competition. Recently, delightful news arrived in my inbox; I was absolutely ecstatic to learn that my entry was shortlisted for the 15 – 18 year old category.

Last night, I attended an amazing awards ceremony, hosted by the RSB, in celebration of the shortlisted and winning entries for the Nancy Rothwell Award as well as the Photography Competition and Outreach and Engagement Awards.

The evening was wonderful and I even had the chance to network with scientists and professionals in a variety of bioscience fields whilst devouring delicious canapés.

I left feeling proud and accomplished but, most of all, inspired.

Of the Kingdom of the Dead

[Warning: due to the nature of this article, there will be graphic images depicting blood]

When you see the term ‘apex predator’, what comes to mind?

Perhaps the more egoistic, yet accurate, response is ‘me’. Humans are highly skilled predators with no natural threat from any other species and that is largely due to our intelligence and ability to form complex social groups. We may not be physically designed to be the best at killing but we have a unique advantage: we kill differently. We have created sophisticated technology to contain, control, and kill animals, we specifically exploit weak and naïve prey, and we even cooperate with other species (such as dogs) to hunt.

Perhaps it is out of modesty (or mild horror at our species’ innate success in killing), but the first creature to come to mind when I think of apex predators is the majestic orca.

 

 

Often referred to as the ‘killer whale’, these cetaceans are clearly not prey; however, this term is a source of misconceptions. Firstly, ‘killer whales’ aren’t even really whales – they are actually dolphins. Furthermore, they are not as ruthlessly violent as the name might suggest and, in fact, there are no confirmed reports of an orca ever preying on or attacking people in their natural habitat – which is surprising when you factor in how poorly humans have treated them. Even the scientific name for this noble beast (Orcinus orca) has strong connotations of murder; the genus name directly translates to ‘of the kingdom of the dead’ and orca is derived from the Latin Orcus (god of the underworld and tormentor of the sinful). A rather harsh name for a species that never hunted us…

That is not to say that orcas do not kill. Orcas are the natural predators of squid, shark, otters, sea lions, penguins, birds, octopi, dolphins, and many other creatures. Their key to success in hunting is two-fold. In part, their success can be attributed to their remarkable design. I have forever been fascinated by the elegant form of the orca; it is an amazingly well-adapted cetacean. Its immensely powerful hypaxial muscles allow it to wield its tail to paralyse prey whilst the streamlined (almost bullet-shaped) body enhances its hydrodynamic movement. But neither these adaptations nor its sharp teeth are what make orcas so lethal.

The killer whale’s weapon of choice is its brain.

Pods of orcas have developed innovative hunting strategies which are passed down through multiple generations and which vary depending on the region and prey. Here are four of their best game plans.

 

Ambush on the Shore. You can’t blame sea lions in the Atlantic to let their guard down once they finally reach the coast of South America- it’s natural for them to assume that their oceanic predators can’t touch them on land. Unfortunately, this is a severe underestimation of the lengths killer whales will go to in order to get their favourite meal. For many of these careless creatures, the façade of security shatters as orcas charge at the shore and beach themselves in an attempt to snatch up a sea lion with its sharp jaws.

 

A Crippling Blow. Even one of the most popular predators and the most vicious of its kind, the great white shark, is not immune to it only natural enemy – the orca. But hunting sharks presents a major threat to the orca as, when it comes to self-defence, great whites have a far superior design to the orca’s typical prey. Rows of glistening, razor-sharp serrated teeth can tear even the thickest whale hide. Orcas must level the playing field if they want to hunt sharks: the killer whale wields its heavy tail, raising it high into the air and crashing it down on the shark’s head before flipping the disoriented victim over with its deft flukes. This complex move forces the shark into a state of “tonic immobility”. Now paralysed, the shark cannot protect itself against its predator – making it a more vulnerable, easy prey.

Orca vs Great White

 

Carousel Feeding. Orcas don’t just pick on creatures their own size; many pods also hunt smaller fish such as mackerel. Hunting smaller creatures does have a major drawback as a few small fish isn’t even a light snack for an orca- in order for the hunt to be worthwhile, they must cause as much carnage as possible. For this reason, orcas work together in small pods to gather hundreds of fish into a tight shoal (a ‘bait ball’) and, when a significant amount of prey is collected in one area, an orca will strike at the bait ball with its tail. The force of this strike stuns and kills the fish – preventing any escapes and allowing the orcas to feed on massive amounts of fish with minimal effort.

Creating a ‘bait ball’

 

Blowhole blocking. Orcas don’t limit themselves to smaller prey either. They are known to orchestrate persistent attacks on enormous cetaceans such as grey, humpback and even blue whales. With a target that can be multiple times larger than themselves, orca pods must first weaken their prey by ramming, biting, and pulling on the whale’s pectoral fins- gradually sapping its strength. Then they launch themselves onto the whale’s back and entirely block its blowhole- suffocating their victim. Eventually, drained of energy and asphyxiated, the exhausted giant drowns.

Orca vs Minke Whale (Credit: National Geographic)

 

These modes of attack, carefully tailored to the prey and situation, reveal the sheer mental capacity that sets the orca apart from the plethora of deadly creatures from the depths of the ocean.

A ruthless, calculating mind is what makes the orca the true predator of predators.

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The featured illustration of this post is a charcoal and pencil sketch of potential anatomy drawings of the orca; I created these sketches in preparation for the Nancy Rothwell Award competition.