An analogy for a paralysing poison
Keith S. Taber
By the light of day…in the dead of night
It was nice to have a sunny and warm day in October to sit in the garden and do some reading. Looking at Chemistry World, I came across an article by Raychelle Burks (2021) on the the natural poison aconitine, extracted from plants collectively known as aconite. The article was punningly called 'The dead of aconite'.
Regular readers of this blog (if that is not a null set) may have noticed my interest in analogies used in teaching and communicating science, and so I was intrigued with the comparison between the effect of the poison and a damaged car engine:
Aconitine likely serves as a defensive tool for the plants that produce it, discouraging [!] predators with its deadly action. It acts quickly on sodium ion signalling channels, opening them and preventing their closure. 'To use a car analogy, if the valves in your car's engine open up, but then won't close, it's dead in the water', wrote toxicologist Justin Bower [sic]. 'Just like aconitine victims.'
Burks, 2021: 69
I was quite interested in following this up, but no citation was given. A little searching around the web led to the a blog called 'Nature's Poisons' written by forensic toxicologist Justin Brower [sic], and an entry on 'the queen of the poisons'.
Making the unfamiliar familiar
Analogy is just one technique used by teachers and others communicating technical or abstract ideas to assist in introducing those ideas – by suggesting that what is unfamiliar and is to be communicated is actually somewhat like something that the listeners(s) or reader(s) already know(s) about.
For this to work, the analogue needs to actually be more familiar than the target idea being communicated. Dr Brower's analogy relies upon people knowing enough about car engines to be familiar with the possibility of engine valves getting stuck open and preventing the car operating.
That the function and operation of the two systems are quite different means that knowing about car engines only offers limited support in learning about the effects of the poison on body cells, but this kind of superficial mapping between systems is true of many teaching analogies. Their role is more about initial familiarisation with the novel concept or phenomenon than providing a detailed explanation. We might almost see their primary role as affective rather than cognitive – making something quite technical seem less alien (and potentially less inaccessible).
Dr Brower explained in his blog that aconitine is found in the plant Monkshood (a.k.a. Wolfsbane), "in every part…from its pretty flowers right down to its dirty roots", and therefore
When any part of the plant is ingested, the aconitine is absorbed through the gut and goes to work. It binds to receptors that help regulate the muscle cells' sodium-ion channels, key components of the nervous system and cardiac cells (i.e. the heart). This action keeps the channels open, allowing sodium to flow freely into the cell. Unable to repolarize, the cells are stuck in a state of "open", and paralysis sets in. To use a car analogy, if the valves in your car's engine open up, but then won't close, it's dead in the water. Just like aconitine victims.
Brower, 2014
Cell membranes have to both prevent the unrestrained ingress and egress of materials, and yet also allow transport of particular substances across the barrier. Sodium ion channels are structures in the cell membrane that are specifically suited to allowing sodium ions (but not, say, calcium ions) to pass through. Moreover these channels do not remain open all the time. (They act as metaphorical 'gates' that can be closed.) The channels depend on specific proteins embedded in the membrane – substances that can have relatively 'large' molecules (that is, large for molecules!) with complex structures. The shapes of proteins can be very complicated.
Molecular shapes
The shapes of simple molecules are understood in terms of the electrical forces within the molecule (and at upper secondary school level the VSEPRT – the valance shell electron pair repulsion theory – model is often taught). Put very simply, the distribution of charges attracting and repelling each other (positive atomic cores, negative electrons) leads to the conformation of lowest potential energy.
The simple molecules can be considered to have one 'central' atomic centre (O in H2O; N in NH3; C in CH4; P in PCl5, and so forth) and the shape decided by considering the electronic distribution around that atom. In a molecule like propane (CH3CH2CH3) the shape can be considered by considering the situation around each of the of the C centres in turn, but taking into account that free rotation around the C-C bonds means that the molecule has a dynamic conformation. In larger molecules, there may be interactions (such as hydrogen bonding) between different parts of the molecule which influence and constrain the shape. Proteins may be very large molecules with many such interactions, often leading to a convoluted shape as the molecule 'folds' according to these interactions. Such protein folding can very difficult to predict.
VSEPRT is used to consider isolated molecules, and ignores the influence of other charges from outside the molecule (such as interactions with solvent molecules). The protein in a context such as a cell membrane may have quite a different shape than the same protein had it been isolated. Moreover, a change in the environment may affect the protein shape. In cells, when the membrane potential changes, the electric field around the ion channel proteins change, and they may change shape. The changes 'open' or 'close' the channels.
If a poison interferes with this process, the channels can no longer control the transport of sodium ions across the membrane in a way that enables the cell's normal functioning. Without this process nerve cells are unable to transmit electrical signals, and heart cells called myocytes (muscle cells) do not beat. That is important, as the beating of the heart is due to the synchronised beating of these cells. And the beating heart keeps the blood flowing, and with it the critical movement of substances (glucose, carbon dioxide, oxygen, etc.) around the body. Aconitine, then, acts as a cardiotoxin and neurotoxin (a heart poison and nerve poison).
The car analogy breaks down in the sense that engine valves that are stuck open might later be closed again with some oil and a hammer and may then function again, and this restoration is not time critical; whereas after a heart has stopped beating, irreversible tissue damage will soon follow.
The first symptoms of aconitine poisoning appear approximately 20 min to 2 hr after oral intake and include paraesthesia [odd sensations], sweating and nausea. This leads to severe vomiting, colicky diarrhoea, intense pain and then paralysis of the skeletal muscles. Following the onset of life-threatening arrhythmia [irregular heartbeat], including ventricular tachycardia [fast, abnormal heartbeat] and ventricular fibrillation [loss of coordination in the muscle activity so there is no effective pumping1] death finally occurs as a result of respiratory paralysis or cardiac arrest.
Beike, Frommherz, Wood, Brinkmann & Köhler,2004: 289
In a worse case scenario for the car, the engine could be replaced, and the car made as good as new. Nonetheless, this is a useful analogy for anyone who knows a little of how the car engine works, as without working valves, the engine cycle (which I seem to recall summarised as 'suck-squeeze-bang-blow' on one course I once taught on) cannot occur, and the car goes nowhere.
Read about making the unfamiliar familiar
| target: sodium channels in cell membrane | analogue: internal combustion engine valves | |
| positive mapping | poison may stop channels closing | valves may stick in open position |
| cell does not function with channels unable to close | engine does not function with valves stuck open | |
| if nerve and heart cells do not function, paralysis occurs, and person dies | if engine does not work, car does not go | |
| negative mapping | tissue damage will soon be irreversible | valves may sometimes be freed up, restoring engine function – a quick response is not critical |
Work cited:
- Beike, J., Frommherz, L., Wood, M., Brinkmann, B., & Köhler, H. (2004). Determination of aconitine in body fluids by LC-MS-MS. International Journal of Legal Medicine, 118(5), 289-293. doi:10.1007/s00414-004-0463-2
- Brower, J. (2014). Aconitine: Queen of poisons. Nature's poisons. Retrieved from https://naturespoisons.com/2014/02/20/aconitine-queen-of-poisons-monkshood/
- Burks, R. (2021). The dead of aconite. Chemistry World (October), 69.
Footnote:
1 An interactive 3D simulation of ventricular fibrillation can be found at https://www.msdmanuals.com/en-gb/home/heart-and-blood-vessel-disorders/abnormal-heart-rhythms/ventricular-fibrillation
