Making molecular mechanisms familiar

A reflection on the pedagogy in Andrew Scott's 'Vital Principles'


Keith S. Taber



Andrew Scott's introduction to the chemistry of the cell is populated by a diverse cast of characters, including ballot machines, beads; blind engineers and blind-folded art-seekers; builders and breaker's yards; cars, freight vehicles and boats; Christmas shoppers, dancers; gatecrashers (despite gatekeepers) and their hosts; invaders, jack-in-the-boxes, legal summonses, light bulbs, mixing bowls, maelstroms, music tapes, office blocks; oceans, seas, rivers, streams, floods and pools; skeletons and their bones, split personalities, springs; sorting offices and postal systems; turnstiles, the water cycle, water wheels, ropes, pulleys and pumps; work benches and work stations; and weeding and seaweed forests.


Scott, A. (1988). Vital Principles. The molecular mechanisms of life. Basil Blackwell.


The task of the popular science writer

This piece is not a formal review of, what is, now, hardly a recent title 1, but a reflection on an example of a science book aimed at – not a specific level of student, but – a more general audience. The author of a 'popular science book' has both a key advantage over the author of many science textbooks, and a challenge. The advantage is being able to define your own topic – deciding what you wish to cover and in how much detail. By contrast, a textbook author, certainly at a level related to formal national examination courses, has to 'cover' the specified material. 2

However the textbook author has the advantage of being able to rely on a fairly well defined model of the expected background of the readership. 3 Students taking 'A level' physics (for example) will be expected to have already covered a certain range of material at a known level through science teaching at school ('G.C.S.E. level') and to have also demonstrated a high level of competence against the school maths curriculum. This is important because human learning is incremental, and interpretive, and so iterative: we can only take in a certain amount of new material at any time, and we make sense of it in terms of our pool of existing interpretative resources (past learning and experiences, etc.) 4


The teacher or textbook author designs their presentation of material based on a mental model of the interpretive resources (e.g., prerequisite learning, familiar cultural referents that may be useful in making analogies or similes, etc.) available to, and likely to be activated in the mind of, the learner when engaging with the presentation.


So, the science teacher works with a model of the thinking of the students, so as to pitch material in manageable learning quanta, that should relate to the prior learning. The teacher's mental model can never be perfect, and consequently teaching-learning often fails (so the good teacher becomes a 'learning doctor' diagnosing where things have gone wrong). However, at least the teacher has a solid starting point, when teaching 11 year olds, or 15 year olds, or new undergraduates, or whatever.

The textbook author shares this, but the popular science author has a potential readership of all ages and nationalities and levels of background in the subject. Presumably the reader has some level of interest in the topic (always helpful to support engagement) but beyond that…

Now the role of the science communicator – be they research scientist with a general audience, teacher, lecturer, textbook author, journalist, documentary producer, or popular science author – is to make what is currently unfamiliar to the learner into something familiar. The teacher needs to make sure the learners both have the prerequisite background for new teaching and appreciate how the new material relates to and builds upon it. Even then, they will often rely on other techniques to make the unfamiliar familiar – such as offfering analogies and similes, anthropomorphism, narratives, models, and so forth.

Read about making the unfamiliar familiar

As the popular science writer does not know about the background knowledge and understanding of her readers, and, indeed, this is likely to be extremely varied across the readership, she has to reply more on these pedagogic tactics. Or rather, a subset of these ways of making the unfamiliar familiar (as the teacher can use gestures, and computer animations, and physical models; and even get the class to role-play, say, electrons moving through a circuit, or proteins binding to enzymes). Thus, popular science books abound with analogies, similes, metaphors and the like – offering links between abstract scientific concepts, and what (the author anticipates) are phenomena or ideas familiar to readers from everyday life. In this regard, Andrew Scott does not disappoint.

Andrew Scott

Scott's website tells us he has a B.Sc. in biochemistry from Edinburgh, and a Ph.D. from Cambridge in chemistry, and that he has produced "science journalism published by academic publishers, newspapers, magazines and websites", and he is an "author of books translated into many languages". I have not read his other books (yet), but thought that Vital Principles did a good job of covering a great deal of complex material – basically biochemistry. It was fairly introductory (so I doubt much could be considered outdated) but nonetheless tackled a challenging and complex topic for someone coming to the book with limited background.

I had a few quibbles with some specific points made – mainly relating to the treatment of underpinning physics and chemistry 5 – but generally enjoyed the text and thinking about the various comparisons the author made in order to help make the unfamiliar familiar to his readership.

Metaphors for molecular mechanisms

Andrew Scott's introduction to the chemistry of the cell is populated by a diverse cast of characters, including ballot machines, beads; blind engineers and blind-folded art-seekers; builders and breaker's yards; cars, freight vehicles and boats; Christmas shoppers, dancers; gatecrashers (despite gatekeepers) and their hosts; invaders, jack-in-the-boxes, legal summonses, light bulbs, mixing bowls, maelstroms, music tapes, office blocks; oceans, seas, rivers, streams, floods and pools; skeletons and their bones, split personalities, springs; sorting offices and postal systems; turnstiles, the water cycle, water wheels, ropes, pulleys and pumps; work benches and work stations; and weeding and seaweed forests.

A wide range of metaphors are found in the book. Some are so ubiquitous in popular science discourse that it may be objected they are not really metaphors at all. So, do "… 'chloroplasts'…trap the energy of sunlight…"? This is a simplification of course (and Scott does go into some detail of the process), but does photosynthesis actually 'trap' the energy of sunlight? That is, is this just a simplification, or is it a figurative use of language? Scott is well aware that energy is not a concept it is easy to fully appreciate,

"Energy is really an idea invented by mankind, rather than some definite thing…

energy can be thought of as some sort of 'force resistance' or 'antiforce' able to counteract the pushes or pulls of the fundamental forces."

pp.25-26

But considerable ingenuity has been used in making the biochemistry of the cell familiar through metaphor:

  • lipids "have split personalities" (and they have 'heads' and 'tails' of course)
  • proteins can "float around within a sea of lipid"
  • proteins are "the molecular workers"
  • the inside of cells can be a "seething 'metabolite pool' – a maelstrom of molecules"; "a swirling sea of chemical activity…the seething sea of metabolism" (so, some appealing alliteration, as well, here 6);
  • the molecules of the cell cytosol are "dancing"
  • "...small compressed springs of ATP, can be used to jack up the chemistry of the cell…"
  • "…thermal motion turns much of the chemical microworld into a molecular mixing bowl."
  • "The membranes of living cells…form a boundary to all cells, and they cordon off specific regions within a cell into distinct organelles."
  • "Some of these gatecrashers within other cells would then have slowly evolved into the mitochondria and chloroplasts of present-day life..."
  • "the 'Ca2+ channels' to open up, this causes Ca2+ ions to flood into the cell …"
  • "the 'ribosomes' … are the chemical automatons"

The figurative flavour of the author's language is established early in the book,

"In a feat of stunning self-regulating choreography, billions of atoms, molecules and ions become a part of the frantic dance we call life. Each revolution of our planet in its stellar spotlight raises a little bit of the dust of earth into the dance of life, while a little bit of the life crumbles back into dust."

p.1

Phew – there is quite a lot going on there. Life is a dance, moreover a frantic dance, of molecular level particles: but not some random dance (though it relies on molecular motion that is said to be a random dance, p.42), rather one that is choreographed, indeed, self-choreographed. Life has agency. It is a dance that is in some sense powered by the revolution of the earth (abound its axis? around its star?) which somehow involves the cycling of dust into, and back out, of life – dust to dust. The reference to a stellar spotlight seems at odds with the Sun as symmetrically radiating in all directions out into the cosmos – the earth moves through that radiation field, but could not escape it by changing orbit. Perhaps this image is meant to refer to how the daily rotation of the earth brings its surface into, and out of, illumination.

So, there is not a spotlight in any literal, sense (the reference to "the central high energy furnace", p.39, is perhaps a more accurate metaphor), but the 'stellar spotlight' is a metaphor that offers a sense of changing illumination.

Similarly, the choreographed dance is metaphorical. Obviously molecules do not dance (a deliberate form of expression), but this gives an impression of the molecular movement within living things. That movement is not choreographed in the sense of something designed by a creator. But something has led to the apparently chaotic movements of billions of molecules and ions, of different kinds, giving rise to highly organised complex entities (organisms) emerging from all this activity. Perhaps we should think of one of those overblown, heavily populated, dance sequences in Hollywood films of the mid 20th century (e.g., as lampooned in Mel Brook's Oscar winning 'The Directors')?

So, in Vital Principles, Scott seeks to make the abstract and complex ideas of science seem familiar through metaphors that can offer a feel for the basic ideas of biochemistry. The use of metaphor in science teaching and other forms of science communication is a well established technique.

Read about science metaphors


Nature and nurture

Later in the book a reader will find that the metaphorical choreographer is natural selection, and natural selection is just the tautological selection of what can best reproduce itself in the environment in which it exists,

"…the brute and blind force of natural selection can be relied upon to weed out the harmful mutations and nurture the beneficial ones. We must always remember, however, that the criterion by which natural selection judges mutations as harmful or beneficial is simply the effect of the mutations on an organism's ability to pass its genetic information on to future generations."

p.182

So, natural selection is a force which is brute and blind (more metaphors) and is able to either weed out (yes, another metaphor) or nurture. That is an interesting choice of term given the popular (but misleadingly over-simplistic) contrast often made in everyday discourse between 'nature' (in the sense of genetics) and 'nurture' (in the sense of environmental conditions). Although natural selection is 'blind', it is said to be able to make judgements.

Form and function in biology

Here we enter one of the major issues in teaching about biology: at one level, that of a naturalistic explanation 7, there is no purpose in life: and anatomical structures, biochemical processes, even instinctive behaviours, have no purpose – they just are; and because they were components of complexes of features that were replicated, they have survived (and have 'survival value').

Yet, it seems so obvious that legs are for walking, eyes are for seeing, and the heart's function is to pump blood around the body. A purist would deny each of these (strictly these suggestions are teleological) and replace each simple statement with a formally worded paragraph completely excluding any reference to, or hint at, purpose.

So, although it seems quite natural to write

"…hormones… are released from one cell to influence the activity of other cells;

…neurotransmitters…are released from nerve cells to transmit a nerve impulse…"

pp.120-121

we might ask: is this misleading?

One could argue that in this area of science we are working with a model which is founded on the theory of natural selection and which posits the evolved features of anatomy, physiology, biochemistry,etc., that increase fitness are analogous to designed and purposeful features that support the project of the continuation of life.

Something that scientists are very quick to deny (that organisms have been designed with purposes in mind) is nevertheless the basis of a useful analogy (i.e., we can consider the organism as if a kind of designed system that has coordinated component parts that each have roles in maintaining the 'living' status of the overall system). We then get the economy of language where

  • hormones and neurotransmitters are released for 'this' purpose, to carry out 'that' function;

being selected (!) over

  • more abstract and complex descriptions of how certain patterns of activity are retained because they are indirectly selected for along with the wider system they are embedded in.

Do scientists sometimes forget they are working with a model or analogy here? I expect so. Do learners appreciate that the 'functions' of organs and molecules in the living thing are only figurative in this sense? Perhaps, sometimes, but – surely -more often, not; and this probably both contributes to, and is encouraged by, the known learning demand of appreciating the "blind [nature of the] force of natural selection".

Scott refers to proteins having a particular task (language which suggests purpose and perhaps design) whilst being clear he is only referring to the outcomes of physical interactions,

"A protein folds up into a conformation which is determined by its amino acid sequence, and which presents to the environment around it a chemical surface which allows the protein to perform its particular chemical task; and the folding and the performance of the task (and, indeed, the creation of the protein in the first place) all proceed automatically governed only by physical laws and forces of nature – particularly the electromagnetic force."

pp.54-55

In practice, biologists and medical scientists – and indeed the rest of us – find it much more convenient to understand organisms in terms of form and function. That is fine if you always keep in mind that natural selection only judges mutations metaphorically. Natural selection is not the kind of entity which can make a judgement, but it is a process that we can conceptualise as if it makes judgements.

This is a difficult balancing act:

"Nature is a blind but a supremely effective engineer. Through the agency of undirected mutation she continually adjusts the structure and the mechanisms of the living things on earth."

p.182

Nature is here treated as if a person: she is an engineer tinkering with her mechanisms. Personification of nature is a long-standing trope, once common among philosophers and not always eschewed by scientists in their writings (e.g., Nicolaus Copernicus, Henri Poincaré, Michael Faraday, even Albert Einstein have personified Nature) – and she is always female.

But usually a competent engineer tinkers according to a plan, or at least with a purpose in mind, whereas nature's tinkering is here described as 'undirected' – it is like she arbitrarily changes the size of a gear or modifies the steam pressure in a cylinder or changes the number of wheels on the locomotive, and then tinkers some more with those that stay on the tracks and manage to keep moving.

Read about personification in science

"All proteins begin life…"

Anthropomorphism: living metaphors

Personification (by referring to her, she, etc.) is not needed to imply entities have some human traits. Indeed, a very common pedagogic technique used when explaining science, anthropomorphism, is to use a kind of metaphorical language which treats inanimate objects or non-human beings as if they are people – as if they can feel, and think, and plan, and desire; and so forth.

  • "Once an enzyme had met and captured the required starting materials …"
  • "Some [non-protein metabolites] act as 'coenzymes', which becomes bound to enzymes and help them to perform their catalytic tasks."
  • "Cells, which had previously been aggressively independent individualists, discovered the advantages of communal life."
  • "descendants of cells which took up residence within other cells and then became so dependent on their hosts, and also so useful to them, that neither hosts nor gatecrashers could afford to live apart."

So, for example, plants are living beings, but do not have a central nervous system and do not experience and reflect on life as people do: so, they do not wish for things,

"…the oxidation of sugars, is also performed by plants when they wish to convert some of their energy stores (largely held in the form of complex carbohydrates) back into ATP."

p.144

Again, such phrasing offers economy of language. Plants do not wish, but any technically correct statement would likely be more complicated and so, arguably, more difficult to appreciate.

Dead metaphors

A key issue in discussing metaphors is that in many cases different readers are likely to disagree over whether a term is indeed being used figuratively or literally. Language is fluid (metaphorically speaking), and a major way language grows is where the need for new terms (to denote newly invented artefacts or newly discovered phenomena) is satisfied by offering an existing term as a metaphor. Often, in time the metaphor becomes adopted as standard usage – so, no longer a metaphor. These examples are sometimes called dead metaphors (or clichéd metaphors). So, for example, at some point, many decades ago, astronomers started to talk of the 'life cycle' of stars which have a moment of 'birth' and eventual 'death'. These metaphors have become so established they are now treated as formal terms in the language of the discipline, regularly used in academic papers as well as more general discourse (see 'The passing of stars: Birth, death, and afterlife in the universe').

So, when Scott writes of "how some micro-organism, say a virus, invades the body…"(p.109) it is very likely most readers will not notice 'invade' as being a metaphor, as this usage is widely used and so probably familiar. The (former?) metaphor is extended to describe selective immune components "binding to foreign invaders [that] can act as a very effective means of defence against disease." These terms are very widely used in discussing infections: though of course there are substantive differences, as well as similarities, with when a country defends itself against actual foreign invaders.

I suspect that considering the lipid bilayer to be "a stable sandwich of two layers of lipid molecules" (p.115) is for many, a dead metaphor. The reference to a DNA double-helix leading to"two daughter double-helices" reflects how atomic nuclei and cells are said to give rise to 'daughters' on fission: again terminology that has become standard in the field.

Sharing a psuedo-explanation for covalent bonding

One phrase that seems to have become a dead metaphor is the notion of electrons being 'shared' in molecules, which "…are formed when their constituent atoms come together to leave at least some of their electrons shared between them" (pp.28-29). Whilst this seems harmless as a description of the structure, it is also used as an explanation of the bonding:

"'hydrogen molecules and water molecules (and all other molecules) are held together by virtue of the fact that electrons are shared between the individual atoms involved, a similarity recognised by saying that in such cases the atoms are held together by 'covalent' bonds.

p.29

But we might ask: How does 'sharing' a pair of electrons explain the molecule being 'held together'? Perhaps a couple with a strained relationship might be held together by sharing a house; or two schools in a confederation by sharing a playing field; or two scuba divers might be held together if the breathing equipment of one had failed so that they only had one functioning oxygen cylinder shared between them?

In these examples, there is of course a sense of ownership involved. Atoms do not 'own' 'their' electrons: the only bonds are electromagnetic; not legal or moral. This may seem so obvious it does not deserve noting: but some learners do come to think that the electrons are owned by specific atoms, and therefore can be given, borrowed, stolen, and so forth, but should ultimately return to their 'own' atom! So, if we acknowledge that there is no ownership of electrons, then what does it even mean for atoms to 'share' them?

So, why would two atoms, each with an electron, become bound by pooling these resources? (Would sharing two houses keep our couple with a strained relationship together; or just offer them a ready way to separate?) The metaphor does not seem to help us understand, but the notion of a covalent bond as a shared electron pair is so well-established that the description commonly slips into an explanation without the explainer noticing it is only a pseudo-explanation (a statement that has the form of an explanation but does not explain anything, e.g., "a covalent bond holds two atoms together because they share a paired of electrons").

Read about types of pseudo-explanation

Elsewhere in the book Scott does explain (if still anthropomorphically) that viable reactions occur because:

"In the new configuration, in other words, the electromagnetic forces of attraction and repulsion between all the electrons and nuclei involved might be more fully satisfied, or less 'strained' than they were before the reaction took place."

p.36

How are metaphors interpreted?

The question that always comes to my mind when I see metaphorical language used in science communication, is how is this understood by the audience? Where I am reading about science that I basically understand reasonably well (and I was a science teacher for many years, so I suspect I cannot be seen a typical reader of such a book) I do reflect on the metaphors and what they are meant to convey. But that means I am often using the familiar science to think about the metaphor, whereas the purpose of the metaphor is to help someone who does not already know the science get a take on it. This leads me to two questions:

  • to what extent does the metaphor give the reader a sense of understanding the science?
  • to what extent does the metaphor support the reader in acquiring an understanding that matches the scientific account?

These are genuine questions about the (subjective and objective) effectiveness of such devices for making the science familiar. There is an interesting potential research programme there.


Shifting to similes

The difference between metaphors and similes is how they are phrased. Both make a comparison between what is being explained/discussed and something assumed to be more familiar. A metaphor describes the target notion as being the comparison (nature is an engineer), but the listener/reader is expected to realise this is meant figuratively, as a comparison. A simile makes the comparison explicit. The comparison is marked – often by the use of 'as' or 'like' as when physicist Max Planck suggested that the law of conservation of energy was "like a sacred commandment".

Read about examples of similes in science

So, when Scott refers to how proteins "act as freight vehicles transporting various chemicals around the body", and "as chemical messages which are sent from one cell to another" (p.10), these are similes.

Springs are used as similes for the interactions between molecules or ions in solids or the bonds within molecules

"…even in solids the constituent molecules and atoms and ions are constantly jostling against one another and often vibrating internally like tiny sub-microscopic springs. All chemical bonds behave a bit like tiny springs, constantly being stretched and compressed as the chemicals they are part of are jostled about by the motion of the other chemicals all around them."

p.39

[Actually the bonds in molecules or crystals are behaving like springs because of the inherent energy of the molecule or lattice: the 'jostling' can transfer energy between molecules/ions and 'springs' so that the patterns of "being stretched and compressed" change, but it is always there. The average amount of 'jostling' depends on the temperature of the material. 5]

In the way the word is usually used in English, jostling is actually due to the deliberate actions of agents – pushing through a crowd for example, so strictly jostling here can be seen as an anthropomorphic metaphor, but the intended meanings seems very clear – so, I suspect many readers will not even have noticed this was another use of figurative language.


One way of marking phrases meant as similes is putting then in inverted commas, so-called scare-quotes, as in

"A rather simple chemical 'cap', for example, is added to the start of the RNA, while a long 'tail' consisting of many copies of the nucleotide A is added to its end…The most significant modifications to the precursor, however, involve the removal of specific portions from the interior [sic] of the RNA molecule, and the joining together of the remaining portions into mature mRNA… This 'splicing' process …"

p.79

Here we have something akin to a cap, and something akin to a tail. As noted above, a difficulty in labelling terms as metaphors or similes is that language is not static, but constantly changing. In science we often see terms borrowed metaphorically from everyday life to label a technical process as being somewhat like something familiar – only for the term to become adopted within the field as a technical term. The adopted terms become literal, with a related, but somewhat different – and usually more precise – meaning in scientific discourse. (This can be the basis of one class of learning impediments as students may not realise the familiar term has specials affordances or restrictions in its technical context.)

Here 'splicing' is marked as a simile – there is a process seen as somewhat similar to how, for example, radio programmes and musical recordings used to be edited by the cutting and resequencing strips of magnetic tape. Yet gene splicing is now widely accepted as a literal use of splicing, rather than being considered figurative. [I suspect a young person who was told about, for example, the Beatles experiments with tape splicing might guess the term is used because the process is like gene splicing!]

The following quote marks a number of similes by placing them within inverted commas:

"The interior of the cell is criss-crossed by a network of structural proteins which is known as the cytoskeleton. The long protein 'bones' of this skeleton are formed by the spontaneous aggregation of many individual globular protein molecules…

Cells use many strong chemical 'pillars' and 'beams' and 'glues' and 'cements', both inside them, to hold the internal structure of cells together, and outside of them, to hold different cells together; but the electromagnetic force is the fundamental 'glue' upon which they all depend."

pp.995-6

Again the phrasing here suggests something being deliberately undertaken towards some end by an active agent (teleology): the cell uses these construction materials for a purpose.

There are various other similes offered – some marked with inverted commas, some with explicit references to being comparisons ('kind of', 'act as', 'sort of', etc.)

  • "…amino acids comprise the chemical 'alphabet' from which the story of protein-based life (i.e., all life on earth) is constructed"
  • "the endoplasmic reticulum is a kind of molecular 'sorting office'"
    • endosomes and lysomes "form a kind of intracellular digestive system and 'breaker's yard'."
    • "Proteins can act as gatekeepers of the cell…"
    • "Proteins can…act as chemical controllers"
    • proteins "can act as defensive weapons"
    • "The proteins which perform these feats are not gates, but 'pumps'..."
    • "Proteins could be described as the molecular workers which actually construct and maintain all cells…"
    • "…proteins are the molecular 'labourers' of life, while genes are the molecular 'manuals' which store the information needed to make new generations of protein labourers"
    • "Membrane proteins often float around within a sea of lipid (although they can also be 'held at anchor' in the one spot if required)"
    • "A ribosome travels down its attached mRNA, a bit like a bead running down a thread (or sometimes like a thread being pulled through a bead)..."
    • "…the 'ribosomes' – molecular 'work-benches' composed of protein and RNA…"
    • Nucleic acids "act as genetic moulds"
    • "the high energy structure of ATP really is very similar to the high energy state of a compressed spring"
    • "Some vital non-protein metabolites act as a sort of 'energy currency'…"

Advancing to analogies

Metaphors and similes point out a comparison, without detailing the nature and limits of that comparison. A key feature of an analogy is there is a 'structural mapping': that is that two systems can be represented as having analogous structural features. In practice, the use of analogy goes beyond suggesting there is a comparison, to specifying, at least to some degree, how the analogy maps onto the target.

Read about examples of analogies in science

Scott employs a number of analogies for readers. He develops the static image of the cell skeleton (met above) with its 'bones', 'pillars' and 'beams' into a dynamic scenario:

"Structural proteins are often referred to as the molecular scaffolding of life, and the analogy is quite apt since so many structural proteins are long fibres or rods; but we think of scaffolding as a static, unchanging, framework. Imagine, however, a structure built of scaffolding in which some of the scaffolding rods were able to slide past one another and then hold the whole framework in new positions."

p.96

Many good metaphors/similes may be based upon comparisons of this type, but they do not become analogies until this is set out, rather than being left to the listener/reader to deduce. For this reason, analogies are better tools to use in teaching than similes as they do not rely on the learners inferring (guessing?) what the points of comparison are intended to be. 8

So, Scott offers the simile of molecules released as 'messengers', but then locates this in the analogy of the postal system, before using another analogy to specify the kind of message being communicated,

"Cells achieve such chemical communication in various ways, but the most vital way is by releasing chemical 'messenger' molecules (the biological equivalent of the postal system, if you like analogies), and many of these messengers are either proteins, or small fragments of proteins."

"A biological messenger molecular is more like a legal summons than a friendly note or some junk mail advertisement – it commands the target cell to react in a precise way to the arrival of the message."

pp.102-103


In the following analogy the mapping is very clear:

"One gene occupies one region of a chromosome containing many genes, much like one song occupies one region of a music tape containing many songs overall."

p.7

Song on music tape is to gene on chromosome


For an analogy to be explicit the mapping between target and analogue must be clear, as here, where Scott spells out how workstations on a production line map onto enzymes,

"The production line analogy is a very good one. The individual 'work stations' are the enzymes, and at these molecular work stations various chemical components are brought together and fashioned into some new component of product. The product of one enzyme can then pass down the line, to become the substrate of the next enzyme, and so on until the pathway is complete."

p.147

Some analogies offer a fairly basic mapping between relatively simple systems:

"If there is lots of A around in the cell, for example, then the rate at which A tends to meet up with enzyme EAB will obviously increase (just as an increase in the number of people you happen to know entering a fairground will increase the chances of you meeting up with someone you know)."

p.150
fairgroundcell
people at a fairgroundmolecules in the cytosol
you at the fairgrounda specific enzyme in the cytosol
people entering the fairground that know you personallymolecules of a type that binds to the specific enzyme
chance of you meeting someone you knowrate of collision between enzyme and the specific molecules it binds to

An analogy with a vote counting machine


Scott compares a nerve cell, the activity of each of which is influenced by a large number of 'input' signals, to a ballot counting machine,

"…most nerve cells receive inputs, in the form of neurotransmitters, from many different cells, so the 'decision' about whether or not the cell should fire depends on the net effect of all the different inputs, some of which will be excitatory, and some inhibitory, with the pattern of input perhaps varying all the time.

So any single nerve cells acts like an [sic] tiny automatic ballot machine, assessing the number of 'yes' and 'no' votes entering it at any one time and either firing or not firing depending on which type of vote predominates at any one time.

…Nerve cells receive electrochemical signals from other cells, and each signal represents a 'yes' or a 'no' vote in an election to determine whether the cell should fire."

pp.166-8


Turnstiles in Alewife station, image from Wikimedia Commons (GNU Free Documentation License)

Scott uses the image of a turnstile, a device that blocks entry unless triggered by a coin or ticket, and which automatically locks once a person has passed through, as a familiar analogue for an ion channel into a cell. The mapping is not spelt out in detail, but should be clear to anyone familiar with turnstiles of this kind,

"When it is sitting in a polarised membrane, this protein is in a conformational state in which it is unable to allow any ions to pass through the cell. When the membrane around it becomes depolarised, however, the protein undergoes a conformational change which causes it briefly to form a channel through which Na+ ions can pass. The channel only remains open for a short time, however, since the conformational upheaval [sic] of the protein continues until it adopts a new conformation in which the passage of Na+ ions is once again blocked. The overall effect of this conformational change is a bit like the operation of a turnstile – it moves from one conformation which prevents anything from passing, into a new conformation which also prevents anything from passing, but in the process of changing from one conformation to another there is a brief period during which a channel allowing passage through is opened up."

p.163

An analogy between a sodium ion channel in a membrane, and a turnstile of the kind sometimes used to give entry to a sporting ground or transport system.


Whether there is an absolute distinction between metaphors/similes and analogies in practice can be debated. So, for example, Scott goes beyond simply suggesting that the nanoscale of molecules is like a mixing bowl, but does not offer a simple mapping between systems,

"Thermal motion turns much of the chemical microworld into a 'molecular mixing bowl' … So the solution of the cytosol acts as an all pervading chemical sea in which many of the chemicals of life are mixed together by random thermal motion as if in a molecular mixing bowl."

p.40

We could see the ocean as a simile (marked by 'acts as an') and the mixing bowl as another (marked by the scare quotes, and then 'as if in a') – but there is a partial mapping with a macroscopic mixing bowl: we are told (i) what is mixed, and (ii) the agent that mixes at the molecular scale, but it is assumed that we already know these should map to (i) the ingredients of a dish being mixed by (ii) a cook.

In places, then, Scott seems to rely on his readers to map features of analogies themselves. For example, in the following (where "The chaos of a large department store on Christmas Eve, or during the January sales, is a reasonable analogy [for the cell, as] there is order and logic within a scene of frantic and often seemingly chaotic activity"), the general point about scale was well made, but (for this reader, at least) the precise mapping remained obscure,

"The frantic chaos of chemistry proceeds too fast and too remotely for us to follow it without great difficulty. We are in the position of airborne observers who see trainloads of shoppers flowing into the city on Christmas Eve morning, and trainloads of the same shoppers laden with purchases flowing back to the suburbs in the evening. From the air we can see the overall effect of suburban shoppers 'reacting' with the shops full of goods, but we remain unaware of the hidden random chaos which allows the reaction to proceed!

p.44

Perhaps other readers immediately see this, but I am not sure what the shoppers are: molecules? but then they are unchanged by reactions? As they flow together into and out of the city (cell?) they could be ions in a nerve cell, but then what are the purchases they carry away (and have they paid for them in energy)? What are the trains? (ion channels? ribosomes?) What are the shops (mitochondria)? Perhaps I am trying to over-interpret an image that is not meant to be specific – but elsewhere Scott seems to have designed his analogies carefully to have specific mappings.


A reference to "a cofactor called 'heme' which actually acts as the chemical vessel on which the oxygen is carried"seems, by itself to be a metaphor, but when read in the context of text that precedes it, seems part of a more developed analogy:

"The most obvious system of bulk transport in the human body is the blood, which flows through our arteries, capillaries and veins like a 'river of life', bringing chemical raw materials (oxygen, water and food) to every cell of the body, and taking waste products away. Within this bulk system, however, the actual job of transporting specific substances is sometimes performed by small 'freighters' such as individual blood cells and even individual protein molecules."

p.98

The precise form of transport acting as an analogue shifts when the discussion shifts from the transport process itself to what I might refer to as the loading and unloading of the 'freighter',

"So the binding of one oxygen molecule to one subunit of an empty [sic] haemoglobin complex greatly encourages the binding of oxygen to the other three available sites. This makes the multi-subunit haemoglobin complex a bit like a four-seater car in which the first person into the car unlocks the door for another three passengers. The crucial step in loading the car is getting the first person in, after which the first person helps all the others to climb aboard.

An opposite effect occurs when loaded haemoglobin reaches a tissue in need of oxygen: the loss of one oxygen molecule from one subunit causes a conformational change in the complex which allows the other three oxygen molecules to be off-loaded much more readily. A suitable analogy to this would be an unstable four-man boat, since, if one man jumps overboard, he may rock the boat sufficiently to make the other three fall out!"

pp.100-101

Why is a child like an office block?

Child is to zygote as office building is to light bulb? (Images from Pixabay)


Scott compares the development of the child from a single cell with a self-assembling office block,

"When a human egg cell begins to divide and create a newborn child it achieves an enlargement equivalent to a lightbulb giving rise to a massive office block 250 metres high; which then, over the next 15 years or so, stretches and widens to an astounding 1,000 metres in height and nearly 250 metres across. In the 'office block' that is you all the plumbing, heating, lighting, telecommunication and ventilation systems were assembled automatically and work together smoothly to sustain a bewildering diversity of very different 'suites' and 'offices'.

p.4

Scott later revisits his office analogy, though now the building is not the growing organism, but just a single cell (one of the 'offices' from the earlier analogy?),

"Cells are not stable and unchanging structures like office blocks. Instead, most parts of a cell are in a state of continual demolition and renewal, known as 'metabolic turnover'. Imagine an office block in which a large team of builders is constantly moving through, knocking down existing walls and using the bricks to build up new ones; ripping apart the furniture and then reassembling it into new forms; peeling off wallpaper, then using it as the raw material to produce new paper which is then put back up again; and all the time some new materials are arriving through the door, to assist in the continual rebuilding, while some of the older materials are constantly being discarded out of the windows. The living cells is in a very similar siltation, with teams of enzymes constantly ripping down the structure of the cell while other teams of enzymes build it up.

Life in the office block imagined earlier might sometimes be a little difficult and chaotic, but at least when change was required it could be brought about quickly, since the necessary tradesmen and supplies would always be on hand; and any mistakes made during the building process could always quickly be put right. Metabolic turnover bestows similar advantages on the living cell."

pp.118-119

The reference to 'teams' of enzymes is another subtle anthropomorphic metaphor. Those in a team are conscious of team membership and coordinate their activities towards a common goal – or at least that is the ideal. Enzymes may seem to be working together, but that is a just a slant we put on processes. Presumably the two sets of teams of enzymes (a catabolic set and an anabolic set) map onto the large team of builders – albeit the enzymes seem to be organised into more specialised working teams than the builders.


Some of Scott's prose, then, combines different ways of making the science familiar, as when he tells the reader

"Water, in other words, is the solvent of life, meaning that it is the liquid which permeates into all the nooks and crannies of the cell and in which all the chemical reactions of life take place. There are various small regions of the cell from which water is excluded, especially within the interior of some large molecules; but the chemistry of life largely proceeds in an ocean of water. It is not a clear ocean – thousands of different types of chemical are dissolved in it, and it is criss-crossed by a dense tangle of giant molecules which form 'fibres' or 'cables' or 'scaffolding' throughout the cell. Swimming through the cell 'cytosol' (the internal 'fluid' of the cell) would be like struggling through a dense underwater forest of seaweed, or through a thick paste or jelly, rather than darting though clear ocean."

p.6

On the molecular level, the water inside of a cell is "an ocean" (a metaphor), which can access the "nooks and crannies of the cell" (a metaphor). The ocean is interrupted by "giant molecules which form 'fibres' or 'cables' or 'scaffolding'…" These terms seem to be used as similes, marked by the use of inverted commas, although Scott also uses this convention to introduce new terms – 'cytosol' is not a simile. Presumably 'fluid' (marked by inverted commas) is being used as a simile as the cytosol is not a pure liquid, but a complex solution.

[The quote implies that "It is not a clear ocean – [as/because] thousands of different types of chemical are dissolved in it", but dissolved solutes would not stop a solution being clear: the actual ocean is very salty, with many different types of ions dissolved in it, but can be clear. Lack of transparency would be due to material suspended, but not actually dissolved, in the water.]

If this is a metaphorical ocean, it is an ocean that would be difficult to swim in, as the tangle of giant molecules is analogous to "a dense underwater forest of seaweed" so it would be like swimming trough "a thick paste or jelly".


The water cycle of life

Perhaps the pièce de résistance in terms of an analogy adopted in the book was the use of a comparison between metabolism and the water cycle,

"I have drawn an analogy between the creation of living things containing many high energy chemicals (i.e. those in which the electromagnetic force is resisted much more than it could be), and the raising water vapour from the sea into the sky. We can continue with this analogy as we look deeper into the energetics of the living cell."

pp.126-127

Scott does indeed develop the analogy, as can be seen from the quotations parsed into the table below:

target conceptanalogue
"…thermodynamic law determines that the energy of the sun must disperse out to the earth and raise the energy level of the things that are found there.
The raw materials of life are some of the things that are found there, and the energy from the sun raises these raw materials up into the higher energy levels associated with organised life,
just as
it raises water up into the sky and deposits some of it in tidy little mountain pools."
"…I have drawn an analogy between
the creation of living things containing many high energy chemicals…
and
the raising water vapour from the sea into the sky."
"The raising of water to the skies is not an isolated and irreversible event, but part of a cycle in which the water eventually loses the energy gained from the sun and returns to the earth as rain, only to absorb some more energy and be lifted up once more, and so on…
Similarly, of course,
the creation of a living being such as yourself is not an isolated and irreversible event, but is part of a cycle of life and death, of growth and decay…"
"If we look inside the chemical mechanisms of the living cell we find that they can harness the energy available in the environment, most of which ultimately comes from the sun,
in a manner similar to
the [person] who has built a water wheel, a pump, a reservoir and many secondary wheels used to power many different tasks…."
"In living things
the roles of
the water-wheels and pumps
are played by
various systems of proteins and membranes,
whilst
the the most common immediate energy reservoir is a chemical known as 'adenosine triphosphate' (ATP).
ATP is the cell's
equivalent of
water stored in a high level reservoir or a tank
because
it takes an energy input to make it, while energy is given out when it breaks apart into ADP and phosphate."
"The considerable resistance to the electromagnetic force embodied in the structure of ATP imposes a strain on the ATP molecule.
It is like
the compressed spring of a jack-in-the-box just waiting to be released;
and when it is released in some appropriate chemical reaction, then the energy level of the molecule falls as it splits up into ADP and phosphate.
Just as the force of water falling from a high gravitational energy level to a lower one can be harnessed to make various energy-requiring processes proceed,
so
the force of an ATP molecule falling from a high chemical energy level to a lower one can be harnessed to make a wide variety of energy-requiring chemical reactions proceed…"
"The ATP manufacturing enzyme
is closely analogous to
a water-wheel,
for
as the hydrogen ions are allowed to flow back through the enzyme,
just as
water flows over a water-wheel,
so
the ensuing chemical reactions 'lift up' the precursors of ATP into their high energy ATP state."
"The principle of such energy coupling
can be understood by the simple analogy of
the water flowing downhill over a water-wheel, and thus serving to turn the wheel and, for example, raise some weight from the ground using a pulley."
"These proteins are the molecular machines
which take the place of
the water-wheels and ropes and pulleys which can couple the falling of water down a mountainside to the lifting of some weight beside the stream"
An extended analogy between two systems

Whether this should be seen as one extended analogy, or more strictly as several, somewhat distinct but related, comparisons is moot, as becomes clear when trying to map out the different features. My best attempt involved some duplication and ambiguity. (Hint to all designers of teaching analogies – map them out as parallel concept maps to help you visualise and keep track of the points being made.)


An analogy (or set of analogies) between biological/biochemical and physical systems


Visualisation – mental simulation

Teaching analogies usually link to what is expected to be (for the members of the audience) a familiar situation, experience, or phenomenon. Readers will be familiar with an office block, or swimming in water.

However, it is also possible for the science communicator to set up an analogy based on a scenario which is unlikely to be familiar, but which can be readily imagined by the reader.

"To appreciate the power of random motion to bring about seemingly purposeful change, imagine a room full of blindfolded people all instructed to walk about at random 'bouncing' off the walls and one another. Imagine also that they have been told to stop moving only when they bump into a small picture hanging from a wall. Finally, suppose that all the pictures are hung in a second room, linked to the room full of people by a narrow open doorway…"

p.40

Few if any readers will have been familiar with this scenario, but the components – groups of people in rooms, blindfolding, adjoining rooms, pictures hung on walls – are all familiar and there is nothing inherently problematic about the scenario even it does not seem very likely. So, here the reader has to build up the analogy from a number of familiar but distinct images.

So, we might consider this a kind of 'gedankenexperiment' or thought experiment – the reader is prompted to consider what would happen if…(and then to transfer what would happen to the target system at the molecular scale). Perhaps some readers immediately 'see' (intuit) what happens in this situation, but otherwise they can 'run' a mental simulation to find out – a technique scientists themselves have used (if probably not regarding blindfolded people in picture galleries).

Analogies only reflect some aspects of the target being compared. The features that map unproblematically are known as the positive analogy, but there is usually a negative analogy as well: features that do not match, and so which would be misleading if carried across. Realistically, the negative analogy will usually have more content than the positive analogy, although much of the negative analogy will be so obviously irrelevant that it is unlikely to confuse anyone.

So, for example, in the analogy the blindfolded people will be wearing clothes, may exchange apologies (or curses) on bumping into each other, and will likely end up bruised – and human nature being what it is, some may cheat by sneaking a look past the edge of the blindfold – but no reader is likely to think these are features that transfer across to the target! Perhaps, however, a reader might wonder if the molecules, like the blindfolded people, are drawing on a source of energy to keep up the activity, and would tire eventually?

There are some other potentially more problematic aspects of the negative analogy. In the thought experiment, the people have been given instructions about what to do, and when to stop, and are acting deliberately. These features do not transfer across, but a reader might not realise this, and could therefore understand the analogy anthropomorphically. It is in situations like this where the teacher can seek feedback on how the analogy is being interpreted (that is, use informal formative assessment), but an author of a book loses control once the manuscript is completed.

Molecular mechanisms made familiar?

There is nothing unusual in Scott's use of metaphor, simile and analogy in seeking to help readers understand abstract scientific ideas. This is an approach common to a good deal of science communication, within and beyond formal teaching. Vital Principles offers many examples, but such devices are common in books seeking to explain science.

I did raise two questions about these techniques above. How do we know if these comparisons are effective in communicating the science? To find out, we would need to talk to readers and question them about their interpretations of the text.

In formal science teaching the focus of such research would likely be the extent to which the presentation supported a learner in acquiring a canonical understanding of the science.

However, as I suggested above, if such research concerned popular science books, we might ask whether the purpose of such books is to teach science or satisfy reader interest. Thus, above, I distinguished an objective and a subjective aspect. If a reader selected a book purely for interest, and is satisfied by what they have read – it made sense to them, and satisfied their curiosity – then does it matter if they may have not understood canonically?

When I read such texts, I wonder about both how a general readership responds to the comparisons offered by authors to make the unfamiliar familiar, and what sense the readers come away with of the science. I guess to some extent popular science authors at least get some level of feedback on the former question – if readers come back for their other titles, then they must be doing something right.

I thought Scott showed a good deal of ingenuity and craft in setting out an account of a challenging and complex area of science – but I would love to know how his different readers interpreted some of his comparisons.


Work cited:

Notes:

1 I have picked up a good many 'popular science books' over the years, but quite a few of them got put on the shelves till I had time to engage with them in any depth. Other things usually got in the way – lesson/lecture preparation being the most demanding imperative for soaking up time over my 'working' life. Retirement has finally allowed me to start going through the shelves…


2 In the English context, perhaps elsewhere, the textbook is now also often expected to not only cover the right content, but follow the examination board's line on the level of treatment, even to the degree of what is acceptable phrasing. Indeed, there are now textbooks associated with the different exam board syllabuses for the 'same' qualification (e.g., A level Chemistry). This seems very unhealthy, and come the revolution


3 The model I am referring to here is the mental model in the teacher's mind of the learner or reader – the background knowledge they have available, their existing level of understanding, the sophistication of their thinking, the range of everyday references they are familiar with which might be useful in making comparisons, their concentration span for dealing with new material or complex language …

If we think of teaching-learning as a system, many system failure (failures of students to understand teaching as intended) can be considered to be due to a mismatch – the teacher's mental model is inaccurate in ways that leads to non-optimal choices in presenting material (Taber, 2001 [Download article]).

This is the basis of the 'learning doctor' approach.

Read about Science learning doctors


4 This is the crux of the so called 'constructivist' perspective on teaching science – a perspective discussed in depth elsewhere on the site.

Read about constructivism


5 There was little in the book I really would have argued with. However, there were a few questionable statements:


"Yet this apparent miracle is completed thousands of times each day throughout the world [in humans], and similar miracles create all manner of simpler creatures, from elephants and birds and flies to bacteria and flowers and mighty oaks."

p.5

This statement seemed to reflect the long-lasting notion of nature as a 'great chain of being' with humans (in the middle of the chain, below a vast range of angelic forms, but) top of the natural world. Bacteria are simpler than humans, I would acknowledge; but I am less sure about flies; even less sure about birds; and question considering trees and other flowering plants, or elephants, as (biologically) simpler than us. This seems an anthropocentric (human-centred), rather than a scientific, take.


"…the periodic table… lists the 92 naturally occurring atoms (plus a few man-made ones) which are the basic raw materials of chemistry…"

p.19

There are clearly more than 92 naturally occurring atoms in the universe. I believe we think there are 90 naturally occurring elements. That is 90 "naturally occurring [kinds of, in the specific sense of proton number] atoms".


Similarly, "a 'compound' is any chemical [sic] composed of two or more atoms chemically bonded together" (pp.29-30) would imply that H2, C60, N2, O2, F2, P4, S8, Cl2, etc are all compounds (when these are elements, not compounds).


Another slightly questionable suggestion was that

"…electrons appear to surround the atomic nucleus, but in a way that allows them to dart to and fro in a seemingly chaotic manner within a particular region of space."

p.21

The notion of electrons darting back and forth does not really reflect the scientific model, but the orbital/quantum model of the atom is subtle and difficult to explain, and was not needed at the level of the description being presented.


A more obvious error was that

"…'heat' is just a measure of the kinetic energy with which particles of matter are moving…"

p.26

In physics, the temperature of a material is considered to reflect the average kinetic energy of the particles (e.g., molecules). But heat is a distinct concept from temperature. Heat is the energy transferred between samples of matter, due to a difference in temperature. So, when Scott writes

"We all know that heat energy moves inevitably from hot places to cold places, and that it will never spontaneously move in the opposite direction."

p.32

this could be seen as a tautology: like saying that imports always come into the county rather than leave – because of how imports are defined.

Although heat and temperature are related concepts, confusing or conflating them is a common alternative conception found among students. Confusing heat with temperature is like confusing a payment into your bank account with the account balance.

Moreover, Scott uses the wrong term when writes,

"[The molecules of?] Chemicals come into contact with one another because they are all constantly moving with the energy we call heat."

p.191

This internal energy that substances have due to the inherent motion of their particles is not heat – it is present even when there is a perfectly uniform temperature throughout a sample (and so no heating going on).


Scott tells readers that "Another name for … a voltage difference is a 'potential difference'…" (p.162) but the term voltage (not voltage difference) normally refers to a potential difference, p.d.. (So, the term voltage difference implies a difference between potential differences, not a difference in potential. If you had one battery with a p.d. across its terminals of 6.0V, and another with a p.d. across its terminals of 4.5V, you could say the 'voltage difference' between the batteries was 1.5V.)


A common alternative conception which Scott seems to share, or at least is happy to reinforce, is the 'fairy tale'* of how ionic bonding results from the transfer of an electron from a metal atom to a neutral non-metal atom,

"When sodium atoms react with chlorine atoms electrons are actually transferred from one atom to the other (see figure [which shows electron transfer from one atom to another]). One electron which is relatively loosely held by a sodium atom can move over to become attached to a chlorine atom."

p.30

This describes a chemically very unlikely scenario (neither sodium nor chlorine are found in the atomic state under normal conditions on earth), and if a sodium atom were to somehow collide with a chlorine atom, the process Scott describes would be thermodynamically non-viable – it requires too much energy to remove even the outermost 'relatively loosely held' electron from the neutral sodium atom. Perhaps this is why in the school laboratory NaCl tends to be prepared from solutions that already contain the sodium ions [NaOH(aq)] and the chloride ions [HCl(aq)].

* For example, read 'A tangible user interface for teaching fairy tales about chemical bonding'

It is hard to be too critical of Scott here, as this account is found in many chemistry text books (and I have even seen it expected in public examinations) although from a scientific point of view, it is a nonsense. That many learners come to think that ionic bonding is due to (or even, 'is') a process of electron transfer is surely a pedagogic learning impediment (Taber, 1994) – a false idea that is commonly taught in school chemistry.

Read more about common misconceptions of ionic bonding


6 As the author of a paper called ' Mediating mental models of metals: acknowledging the priority of the learner's prior learning', I must confess to being somewhat partial to some decent alliteration.


7 Many scientists will believe there is a purpose underpinning the evolution of life on earth, and will see creation as the unfolding of a supernatural plan. (Some others will vehemently reject this. Others still will be agnostic.) However, natural science is concerned with providing natural explanations of the world in terms of natural mechanisms. Even if a scientist thinks things are the way they are because that is God's will, that would be inadmissible as a scientific argument, as it does not explain how things came about through natural processes.

Read more about science and religion


8 Teaching, or for that matter writing a science book, is informed by the teacher's/author's mental model of how the reader/listener will make sense of the text (see above). How they actually make sense of the text depends on the interpretive resources they have available, and bring to mind, and it is common for learners/readers not to interpret texts in the way intended – often they either do not make sense of the information, or make a different sense to that intended. A teacher who is a 'learning doctor' can seek to diagnose and treat these 'teaching-learning system failures' when they inevitably occur, but teachers can avoid a good many potential problems by being as explicit as possible and not relying on learners to spontaneously make intended associations with prior learning or cultural referents.

Read about being a learning doctor

As suggested above, authors have an even more challenging task as their readerships may have a diverse range of prior knowledge and other available interpretive resources (e.g., a popular television programme or pop star in one country may be unknown to readers from another); and the author cannot check they have been understood as intended, in the way a teacher usually can.


How much damage can a couple of molecules do?

Just how dangerous is Novichok?

Keith S. Taber


"We are only talking about molecules here…

There might be a couple of molecules left in the Salisbury area. . ."

Expert interviewed on national news

The subject of chemical weapons is not to be taken lightly, and is currently in the news in relation to the Russian invasion of Ukraine, and the concern that the limited progress made by the Russian invaders may lead to the use of chemical or biological weapons to supplement the deadly enough effects of projectiles and explosives.

Organophosphorus nerve agents (OPNA) were used in Syria in 2013 (Pita, & Domingo, 2014), and the Russians have used such nerve agents in illicit activities – as in the case of the poisoning of Sergey Skripal and his daughter Yulia in Salisbury. Skripal had been a Russian military intelligence officer who had acted for the British (i.e., as a double agent), and was convicted of treason – but later came to the UK in a prisoner swap and settled in Salisbury (renown among Russian secret agents for its cathedral). 1

Salisbury, England – a town that featured in the news when it was the site of a Russian 'hit' on a former spy (Image by falco from Pixabay )

These substances are very nasty,

OPNAs are odorless and colorless [and] act by blocking the binding site of acetylcholinesterase, inhibiting the breakdown of acetylcholine… The resulting buildup of acetylcholine leads to the inhibition of neural communication to muscles and glands and can lead to increased saliva and tear production, diarrhea, vomiting, muscle tremors, confusion, paralysis and even death

Kammer, et al., 2019, p.119

So, a substance that occurs normally in cells, but is kept in check by an enzyme that breaks it down, starts to accumulate because the enzyme is inactivated when molecules of the toxin bind with the enzyme molecules stopping them binding with acetylcholine molecules. Enzymes are protein based molecules which rely for their activity on complex shapes (as discussed in 'How is a well-planned curriculum like a protein?' .)


Acetylcholine is a neurotransmitter. It allows signals to pass across synapses. It is important then that acetylcholine concentrations are controlled for nerves to function (Image source: Wikipedia).


Acetylcholinesterase is a protein based enzyme that has an active site (red) that can bind and break up acetylcholine molecules (which takes about 80 microseconds per molecule). The neurotransmitter molecule is broken down into two precursors that are then available to be synthesised back into acetylcholine when appropriate. 2

Toxins (e.g., green, blue) that bind to the enzyme's active site block it from breaking down acetylcholine.

(Image source: RCSB Protein Data Bank)


A need to clear up after the release of chemical agents

The effects of these agents can be horrific – but, so of course, can the effects of 'conventional' weapons on those subjected to aggression. One reason that chemical and biological weapons are banned from use in war is their uncontrollable nature – once an agent is released in an environment it may remain active for some time – and so hurt or kill civilians or even personnel from the side using those weapons if they move into the attacked areas. The gases used in the 1912-1918 'world' war, were sometimes blown back towards those using them when the wind changed direction.


Image by Eugen Visan from Pixabay 

This is why, when small amounts of nerve agents were used in the U.K. by covert Russian agents to attack their targets, there was so much care put into tracing and decontaminating any residues in the environment. This is a specialised task, and it is right that the public are warned to keep clear of areas of suspected contamination. Very small quantities of some agents can be very harmful – depending upon what we mean by such relative terms as 'small'. Indeed, two police officers sent to the scene of the crime became ill. But what does 'very small quantities' mean in terms of molecules?

A recent posting discussed the plot of a Blakes7 television show episode where a weapon capable of destroying whole planets incorporated eight neutrons as a core component. This seemed ridiculous: how much damage can eight neutrons do?

But, I also pointed out that, sadly, not all those who watched this programme would find such a claim as comical as I did. Presumably, the train of thought suggested by the plot was that a weapon based on eight neutrons is a lot more scary than a single neutron design, and neutrons are found in super-dense neutron stars (which would instantly crush anyone getting too near), so they are clearly very dangerous entities!

A common enough misconception

This type of thinking reflects a common learning difficulty. Quanticles such as atoms, atomic nuclei, neutrons and the like are tiny. Not tiny like specs of dust or grains of salt, but tiny on a scale where specs of dust and grains of salt themselves seem gigantic. The scales involves in considering electronic charge (i.e., 10-19C) or neutron mass (10-27 kg) can reasonably be said to be unimaginatively small – no one can readily visualise the shift in scale going from the familiar scale of objects we normally experience as small (e.g., salt grains), to the scale of individual molecules or subatomic particles.

People therefore commonly form alternative conceptions of these types of entities (atoms, electrons, etc.) being too small to see, but yet not being so far beyond reach. It perhaps does not help that it is sometimes said that atoms can now be 'seen' with the most powerful microscopes. The instruments concerned are microscopes only by analogy with familiar optical microscopes, and they produce images, but these are more like computer simulations than magnified images seen through the light microscope. 3

It is this type of difficulty which allows scriptwriters to refer to eight neutrons as being of some significance without expecting the audience to simply laugh at the suggestion (even if some of us do).

An expert opinion

Although television viewers might have trouble grasping the insignificance of a handful of neutrons (or atoms or molecules), one would expect experts to be very clear about the vast difference in scale between us (people for example) and them (nanoscopic entities of the molecular realm). Yet experts may sometimes be stretched beyond their expertise without themselves apparently being aware of this – as when a highly qualified and experienced medical expert agreed with an attorney that the brain sends out signals to the body faster than the speed of light. If a scientific expert in a high profile murder trial can confidently make statements that are scientifically ridiculous then this underlines just how challenging some key scientific ideas are.

For any of us, knowing what we do not know, recognising when we are moving outside out of areas where we have a good understanding, is challenging. Part of the reason that student alternative conceptions are so relevant to science learning is that a person's misunderstanding can seem subjectively to be just as well supported, sensible, coherent and reasonable as a correct understanding. Where a teacher themself has an alternative conception (which sometimes happens, of course) they can teach this with as much enthusiasm and confidence as anything they understand canonically. Expertise always has limitations.

A chemical weapons expert

I therefore should not have been as surprised as I was when I heard a news broadcast featuring an expert who was considered to know about chemical weapons refer to the potential danger of "a couple of molecules". This was in relation to the poisoning by Russian agents of the Salisbury residents,

"During an interview on a BBC Radio 4 news programme (July 5th, 2018), Hamish de Bretton-Gordon, who brands himself as one of the world's leading chemical weapons experts, warned listeners that there may be risks to the public due to residue from the original incident in the area. Whilst that may have been the case, his suggestion that "we are only talking about molecules here. . .There might be a couple of molecules left in the Salisbury area. . ." seemed to suggest that even someone presented to the public as a chemistry expert might completely fail to appreciate the submicroscopic scale of individual molecules in relation to the macroscopic scale of a human being."

Taber, 2019, p.130
Chemical weapons expert ≠ chemistry expert

Now Colonel de Bretton-Gordon is a visiting fellow at  Magdalene College Cambridge, and the College website describes him as "a world-leading expert in Chemical and Biological weapons". I am sure he is, and I would not seek to underplay the importance of decontamination after the use of such agents; but if someone who has such expertise would assume that a couple of molecules of any substance posed a realistic threat to a human being with its something like 30 000 000 000 000 cells, each containing something like 40 000 000 molecules of protein (to just refer to one class of cellular components), then it just underlines how difficult it is to appreciate the gulf in scale between molecules and men.

Regarding samples of nerve agents, they may be deadly even in small quantities, but that still means a lot of molecules.

Novichok cocktails

The attacks in Salisbury (from which the intended victims recovered, but another person died in nearby Amesbury apparently having come into contact with material assumed to have been discarded by the criminals), were reported to have used 'Novichok', a label given to group of compounds.

"Based on analyses carried out by the British "Defence Science and Technology Laboratory" in Porton Down it was concluded that the Skripals were poisoned by a nerve agent of the so-called Novichok group. Novichok … is the name of a group of nerve agents developed and produced by Russia in the last stage of the Cold War."

Carlsen, 2019, p.1

Testing of toxins is often based on the LD50 – which means finding the dose that has an even chance of being lethal. This is not an actual amount, as clearly the amount of material that is needed to kill a large adult will be more than that to kill a small child, but the amount of the toxin needed per unit mass of victim. Although no doubt these chemicals have been directly tested on some poor test specimens of non-consenting small mammals, such information is not in the public domain.

Indeed, being based on state secrets, there is limited public data on Novichok and related agents. Carlsen (2019) estimates the LD50 for oral administration of 9 compounds in the Novichok group and some closely related agents to vary between 0.1 to 96.16 mg/kg.

Carlsen suggest the most toxic of these compounds is one known as VX. VX was actually first developed by British Scientists, although almost equivalent nerve agents were later developed elsewhere, including Russia.


'Chemical structures of V-agents.'
(Figure 2 from Nepovimova & Kuca, 2018 – subject to http://creativecommons.org/licenses/BY-NC-ND/4.0/)
n.b. This figure shows more than a couple of molecules of nerve agent – so might this be a lethal dose?


Carlsen then argues that the actual compounds in Novachok are probably less toxic than XV, which might explain…

"…why did the Skripals not die following expose to such high potent agents; just compare to the killing of Kim Jong-nam on February 13, 2017 in Kuala Lumpur International Airport, where he was attacked by the highly toxic VX, and died shortly after."

Carlsen, 2019, p1

So, for the most sensitive agent, known as XV (LD50 c. 0.1 mg/kg), a person of 50 kg mass would it is estimated have a 50% chance of being killed by an oral dose of 0.1 x 50 mg. That is 5 mg or 0.005 g by mouth. A single drop of water is said to have a volume of about 0.05 ml, and so a mass of about 0.05 g. So, a tenth of a drop of this toxin can kill. That is a very small amount. So, if as little as 0.005 g of a nerve agent will potentially kill you then that is clearly a very toxic substance.

The molecular structure of XV is given in the figure above taken from Nepovimova and Kuca (2018). These three structures shown appear to be isomeric – that is the three molecules are structural isomers. They would have the same empirical formula (and the same molecular mass).

Chemical shorthand

This type of structural formula is often used for complex organic molecules as it is easy for experts to read. It is one of many special types of representation used in chemistry. It is based on the assumption that most organic compounds can be understood as if substituted hydrocarbons. (They may or may not be derived that way – this is jut a formalism used as a thinking tool.) Hydrocarbons comprise chains of carbon atomic cores bonded to each other, and with their other valencies 'satisfied' by being bonded to hydrogen atomic cores. These compounds can easily be represented by lines where each line shows the bond between two carbon atomic cores. The hydrogen centres are not shown at all, but are implicit in the figure (they must be there to 'satisfy' the rules of valency – i.e., carbon centres in a stable structures nearly always have four bonds ).

Anything other than carbon and hydrogen is shown with elemental symbols, and in most organic compounds these other atomic centres take up on a minority of positions in the structure. So, for compounds, such as the 'VX' compounds, these kinds of structural representations are a kind of hybrid, with some atomic centres shown by their elemental symbols – but others having to be inferred.

From the point of view of the novice learner, this form of abstract representation is challenging as carbon and hydrogen centres need to be actively read into the structure (whereas an expert has learnt to do this automatically). But for the expert this type of representation is useful as complex organic molecules can contain hundreds or thousands of atomic centres (e.g., the acetylcholinesterase molecule, as represented above) and structural formulae that show all the atomic centres with elemental symbols would get very crowded.

So, below I have annotated the first version of XV:


The VX compound seems to have a molecular mass of 267

This makes the figure much more busy, but helps me count up the numbers of different types of atomic centres present and therefore work out the molecular mass – which, if I had not made a mistake, is 267. I am working here with the nearest whole numbers, so not being very precise, but this is good enough for my present purposes. That means that the molecule has a mass of 267 atomic mass units, and so (by one of the most powerful 'tricks' in chemistry) a mole of this compound, the actual substance, would have a mass of 267g.

The trick is that chemists have chosen their conversion factor between molecules and moles, the Avogadro constant of c. 6.02 x 1023, such that adding up atomic masses in a molecule gives a number that directly scales to grammes for the macroscopic quantity of choice: the mole. 5

So, if one had 267 g of this nerve agent, that would mean approximately 6.02 x 1023 molecules. Of course here we are talking about a much smaller amount – just 0.005 g (0.005/267, about 0.000 02 moles) – and so many fewer molecules. Indeed we can easily work out 0.005 g contains something like

(0.005 / 267) x 6.02 x 1o23 = 11 273 408 239 700 374 000 = 1×1019 (1 s.f.)

That is about

10 000 000 000 000 000 000 molecules

So, because of the vast gulf in scale between the amount of material we can readily see and manipulate, and the individual quanticle such as a molecule, even when we are talking about a tiny amount of material, a tenth of a drop, this still represent a very, very large number of molecules. This is something chemistry experts are very aware of, but most people (even experts in related fields) may not fully appreciate.

The calculation here is approximate, and based on various estimates and assumptions. It may typically take about 10 000 000 000 000 000 000 molecules of the most toxic Novichok-like agent to be likely to kill someone – or this estimate could be seriously wrong. Perhaps it takes a lot more, or perhaps many fewer, molecules than this.

But even if this estimate is out by several orders of magnitude and it 'only' takes a few thousand million million molecules of XV for a potential lethal dose, that can in no way be reasonably described as "a couple of molecules".

It takes very special equipment to detect individual quanticles. The human retina is in its own way very sophisticated, and comes quite close to being able to detect individual photons – but that is pretty exceptional. As a rule of thumb, when anyone tells us that a few molecules or a few atoms or a few ions or a few electrons or a few neutrons or a few gamma rays or… can produce any macroscopic effect (that we can see, feel, or notice) we should be VERY skeptical.


Work cited:

Notes:

1 Two men claiming to be the suspects whose photographs had been circulated by the British Police, and claimed by the authorities here to be Russian military intelligence officers, appeared on Russian television to explain they were tourists who had visited Salisbury sightseeing because of the Cathedral.

2 According to the RCSB Protein Data Bank website

"Acetylcholinesterase is found in the synapse between nerve cells and muscle cells. It waits patiently and springs into action soon after a signal is passed, breaking down the acetylcholine into its two component parts, acetic acid and choline."

Molecule of the month: Acetylcholinesterase

Of course, it does not 'wait patiently': that is anthropomorphism.


3 We might think it is easy to decide if we are directly observing something, or not. But perhaps not:

"If a chemist heats some white powder, and sees it turns yellow, then this seems a pretty clear example of direct observation. But what if the chemist was rightly conscious of the importance of safe working, and undertook the manipulation in a fume cupboard, observing the phenomenon through the glass screen. That would not seem to undermine our idea of direct observation – as we believe that the glass will not make any difference to what we see. Well, at least, assuming that suitable plane glass of the kind normally used in fume cupboards has been used, and not, say a decorative multicoloured glass screen more like the windows found in many churches. Assuming, also, that there is not bright sunlight passing through a window and reflecting off the glass door of the fume cupboard to obscure the chemist's view of the powder being heated. So, assuming some basic things we could reasonably expect about fume cupboards, in conjunction with favourable viewing conditions, and taking into account our knowledge of the effect of plane glass, we would likely not consider the glass screen as an impediment to something akin to direct observation.

Might we start to question an instance of direct observation if instead of looking at the phenomenon through plane glass, there was clear, colourless convex glass between the chemist and the powder being heated? This might distort the image, but should not change the colours observed. If the glass in question was in the form of spectacle lenses, without which the chemist could not readily focus on the powder, then even if – technically – the observations were mediated by an instrument, this instrument corrects for a defect of vision such that our chemist would feel that direct observation is not compromised by, but rather requires, the glasses.

If we are happy to consider the bespectacled chemist is still observing the phenomenon rather than some instrumental indication of it, then we would presumably feel much the same about an observation being made with a magnifying glass, which is basically the same technical fix as the spectacles. So, might we consider observation down a microscope as direct observation? Early microscopes were little more than magnifying glasses mounted in stands. Modern compound microscopes use more than one lens. A system of lenses (and some additional illumination, usually) reveals details not possible to the naked eye – just as the use of convex spectacles allow the longsighted chemist to focus on objects that are too close to see clearly when unaided.

If the chemist is looking down the microscope at crystal structures in a polished slice of mineral, then, it may become easier to distinguish the different grains present by using a Polaroid filter to selectively filter some of the light reaching the eye from the observed sample. This seems a little further from what we might normally think of as direct observation. Yet, this is surely analogous to someone putting on Polaroid sunglasses to help obtain clear vision when driving towards the setting sun, or donning Polaroid glasses to help when observing the living things at the bottom of a seaside rock pool on a sunny day when strong reflections from the surface prevent clear vision of what is beneath.

A further step might be the use of an electron microscope, where the visual image observed has been produced by processing the data from sensors collecting reflections from an electron beam impacting on the sample. Here, conceptually, we have a more obvious discontinuity although the perceptual process (certainly if the image is of some salt crystal surface) may make this seem no different to looking down a powerful optical microscope. An analogy here might be using night-vision goggles that allow someone to see objects in conditions where it would be too dark to see them directly. I have a camera my late wife bought me that is designed for catching images of wildlife and that switches in low light conditions to detecting infrared. I have a picture of a local cat that triggered an image when the camera was left set up in the garden overnight. The cat looks different from how it would appear in day-light, but I still see a cat in the image (where if the camera had taken a normal image I would not have been able to detect the cat as the image would have appeared like the proverbial picture of a 'black cat in a coal cellar'). Someone using night-vision goggles considers that they see the fox, or the escaped convict, not that they see an image produced by electronic circuits.

If we accept that we can see the cat in the photograph, and the surface details of crystal grains in the electron microscope image, then can we actually see atoms in the STM [scanning tunneling microscope] image? There is no cat in or on my image, it is just a pattern of pixels that my brain determines to represent a cat. I never saw the cat directly (I was presumably asleep) so I have no direct evidence there really was a cat if I do not accept the photograph taken using infrared sensors. I believe there are cats in the world, and have seen uninvited cats in my garden in daylight, and think the camera imaged one of them at night. So it seems reasonable I am seeing a cat in the image, and therefore I might wonder if it is reasonable to doubt that I can also see atoms in an STM image.

One could shift further from simple sensory experience. News media might give the impression that physicists have seen the Higgs boson in data collected at CERN. This might lead us to ask: did they see it with their eyes? Or through spectacles? Or using a microscope? Or with night-vision goggles? Of course, they actually used particle detectors.

Feyerabend suggests that if we look at cloud chamber photographs, we do not doubt that we have a 'direct' method of detecting elementary particles …. Perhaps, but CERN were not using something like a very large cloud chamber where they could see the trails of condensation left in the 'wake' of a passing alpha particle, and that could be photographed for posterity. The detection of the Higgs involved very sophisticated detectors, complex theory about the particle cascades a Higgs particle interaction might cause, and very complex simulations to allow for all kinds of issues relating to how the performance of the detectors might vary (for example as they age) and how a signal that might be close to random noise could be identified…. No one was looking at a detector hoping to see the telltale pattern that would clearly be left by a Higgs, and only a Higgs. In one sense, to borrow a phrase, 'there's nothing to see'. Interpreting the data considered to provide evidence of the Higgs was less like using a sophisticated microscope, and more like taking a mixture of many highly complex organic substances, and – without any attempt to separate them – running a mass spectrum, and hoping to make sense of the pattern of peaks obtained.

Taber, 2019, pp.158-160

4 That is not to suggest that one should automatically assume that one molecule of a toxin can only ever damage one protein molecule somewhere in one body cell. After all, one of the reasons that CFCs (chlorofluorocarbons, which used to be used as propellants in all kinds of spray cans for example) were so damaging to the ozone 'layer' was because they could initiate a chain reaction.

In reactions that involve free radicals, each propagation step can produce another free radical to continue the reaction. Eventually two free radicals are likely to interact to terminate the process – but that might only be after a great many cycles, and the removal of a great many ozone molecules from the stratosphere. However, even if one free radical initiated the destruction of many molecules of ozone, that would still be a very small quantity of ozone, as molecules are so tiny. The problem was of course that a vast number of CFC molecules were being released.


5 So one mole of hydrogen gas, H2, is 2g, and so forth.

How is a well-planned curriculum like a protein?

Because it has different levels of structure providing functionality

Keith S. Taber

I have been working on a book about pedagogy, and was writing something about sequencing teaching. I was setting out how well-planned teaching has a structure that has several levels of complexity – and I thought a useful analogy here (as the book is primarily aimed at chemistry educators) might be protein structure.

Proteins can have very complex structures. (Image by WikimediaImages from Pixabay )

Proteins are usually considered to have at least three, or often four, levels of structure. Protein structure is not just of intellectual interest, but has critical functional importance. It is the shape, conformation, of the protein molecule which allows it to have its function. Now, I should be careful here, as I am well aware (and have discussed on the site) how the language we often use when discussing organisms can seem teleological.

Read about teleology

We analyse biological structures and processes, and when considering the component parts can see them as having some function in relation to that overall structure or process. That can give the impression of purpose – as though someone designed the shape of the protein with a particular function in mind. That can give the impression of teleological thinking – seeing nature as having a purpose. The scientific understanding is that proteins with their complex shapes that are just right for their observed functions have been subject to natural selection over a very long period – evolving along with the structures and processes they are part of.

The importance of protein shape

The shape of a protein can allow it to act as a catalyst that will allow, say, a polysaccharide to break down into simple sugars at body temperature and at a rate that can support an organism's metabolism (when the rate without the enzyme would only give negligible amounts of product ). The shape of a protein, as in haemoglobin, may allow a complex to exist which either binds with oxygen or releases it depending on the local conditions in different parts of the body. And so forth.

Now, chemically, proteins are of the form of polyamides – substances that can be understood to have a molecular structure of connected amide units (above left, source: Wikipedia) in a long chain that results from polymerising amino acid units (amino acid structure shown above right, source: Wikipedia). An amino acid molecule has two functional groups – an amide group (-NH2) which allows the compounds to react with carboxylic acids (including amino acids for example), and a carboxylic acid group (-COOH) that allows the compound to react with amides (including amino acids for example). So, amino acids can polymerise as each amino acid molecule has two sites that can be loci for the reaction.

Molecular structure of a compound formed by four amino acids – the peptide linkage (highlighted orange) is formed from part (-CO-) of the acid group (-COOH, as outlined in red) of one amino acid molecule with part (-NH-) of the amine group (-NH2, as outlined in cyan) of another amino acid molecule (which may be of the same or a different amino acid). In proteins the chains are much longer. Original image from Wikipedia

Special examples of polyamides

So, proteins are polyamides. But this does not mean that polyamides are proteins. In the same way that chemistry Nobel prize winners are scientists – but not all scientists are Nobel laureates. So, being a polyamide is a necessary, but not a sufficient, condition for being a protein. For examples, nylons are also polyamides, but are not proteins. 1

Proteins tend to be very complex polyamides, which are built up from a number of different amino acids (of which 20 are found in proteins). Each amino acid has a different molecular structure – there is the common feature which allows the peptide linkages to form, but each amino acid also has a different side chain or 'residue' as part of its molecule. But just being a large, complex, polypeptide built from a selection of those 20 amino acids does not necessarily lead to a protein found in livings things. The key point about the protein is that its very specific shape allows it to have the function it does. Indeed there are many billions of polyamide structures of similar complexity to naturally found proteins which could exist (and perhaps do somewhere), but which have no role in living organisms (on this planet at least!)

A simple teaching analogy often used to explain enzyme specificity is that of a lock and key. Whilst somewhat simplistic, if we consider that the protein has to have just the right shape to 'fit' the 'substrate' molecule then it is clear that the precise shape is important. A key that opens a door lock has to be precisely shaped. (The situation with an enzyme is actually more demanding, as the molecule can change its shape according to whether a substrate is bound – so it needs to be the right shape to bind to the substrate molecular and then the right shape to release the product molecule.)

So a functioning protein molecule has a very specific shape, indeed sometimes a specific profile of shapes as it interacts with other molecules, and this can be understood to arise from several levels of structure.

Four levels of structure

The primary structure is the sequence of amino acid residues along the polypeptide skeleton.

The amino acid sequence in polypeptide chains in human insulin (with the amino acids represented by conventional three letter abbreviations) – image from Saylor Academy, 2012 open access text: The Basics of General, Organic, and Biological Chemistry

The chain is not simply linear, or a zigzag shape (as we might commonly represent an organic molecules based on a chain of carbon atoms). Rather the interactions between the peptide units, causes the chain to form a more complex three-dimensional structure, such as a helix. This is the secondary structure.

Protein chains tend to form into shapes such as helices (This example: Crystal structure of the DNA-binding protein Sso10a from Sulfolobus solfataricus; from the protein data base PDB DOI: 10.2210/pdb4AYA/pdb.)

Because the secondary structure allows the amino acid residues on different parts of the chain to be close, interactions, forms of bonding, form between different points on the chain. (As shown in the representation of the insulin structure above.) This depends on the amino acid sequence as the different residues have different sizes, shapes and functional groups – so interactions will occur between particular residue pairs. This adds another level of structure.

A coiled cable can take on various overall shapes (Image by Brett Hondow from Pixabay )

Imagine taking a coiled cable somewhat like the helical secondary structure), such as used for some headphone, and folding this into a more complex shape. This is the tertiary structure, and gives the protein its unique shape, which it turn makes it suitable to act as an enzyme or hormone or whatever.

Proteins may be even more complex, as they may comprise complexes of several chains, closely bound together by weak chemical bonds. Haemoglobin, for example, has four such subunits arranged in a quaternary structure.

A representation of the structure of a haemoglobin protein – with the four interlinked chains shown in different colours (Structure determination of haemoglobin from Donkey (equus asinus) at 3.0 Angstrom resolution, from the protein data base: PDB DOI: 10.2210/pdb1S0H/pdb)

But what has this got to do with sequencing curriculum?

When planning teaching, such as when developing a course or writing a 'scheme of work', one has to consider how to sequence the introduction of course material as well as learning activities. This can be understood to have different levels in terms of the considerations we might take into account.

A well-designed curriculum sequence has several levels of structure (ordering, building, cross-linking) affording more effective teaching

Primary structure and conceptual analysis

A fundamental question (once we have decided what falls within the scope of the course, and selected the subject matter) is how to order the introduction of topics and concepts. There is usually some flexibility here, but as some concepts are best understood in terms of other more fundamental ideas, there are more and less logical ways to go about this. 'Conceptual analysis' is the technique which is used to break down the conceptual structure of material to see what prerequisite learning is necessary before discussing new material.

For example, if we wish to teach for understanding then it probably does not make sense to introduce double bonds before the concept of covalent bonds, or neutralisation before teaching something about acids, or d-level splitting before introducing ideas about atomic orbitals, or the rate determining step of a reaction before teaching about reaction rate. In biology, it would not make sense to teach about mitochondria before the concept of cells had been introduced. In physics, one would not seek to teach about conservation of momentum, before having introduced the concept of momentum. The reader can probably think of many more examples. The sequence of quanta of subject matter in the curriculum sequence can be considered a first level of curriculum structure.

Secondary structure and the spiral curriculum

We also revise topics periodically at different levels of treatment. We introduce topics at an introductory level – and later offer more sophisticated accounts (atomic structure, acidity, oxidation…). We distinguish metals form non-metals and later introduce electronegativity. We distinguish ionic and covalent bonds and later introduce degrees of bond polarity. In recent years this has been reflected in the work on developing model 'learning progressions' that support students in more sophisticated scientific thinking over several grade levels.

From Taber, 2021

This builds upon the well-established idea of a 'spiral curriculum' (Bruner, 1960) where the learner resists topics in increasing levels of sophistication over their student career. So, here is a level of structure beyond the linear progression of topics covered in different sessions, encompassing revisiting the same topic at different turns of the 'spiral' (perhaps like the alpha helices formed in may proteins).

This already suggests there will be linkages across the 'chain' of teachings units (whether seen as lectures/lesson or lesson episodes) as references are made back to earlier teaching in order to draw upon more fundamental ideas in building up more complex ideas, and building on simplified accounts to develop more nuanced and sophisticated accounts.

Tertiary structure – drip feeding to reinforce learning

The skilled teacher will also be making other links that are not strictly* essential but are useful unless the students have exemplary study skills usually ARE essential!]

To support students in consolidating learning (something that is usually essential if we want them to remember the material and be able to apply it months later) the teacher will 'drip feed' reinforcement of prior learning by looking for opportunities to revise key points form earlier teaching.

We have defined what we mean by 'compound' or 'oxidising agent' or 'polymer', so now we spot opportunities to reinforce this whenever it seems sensible to do so in teaching other material. We have taught students to calculate molecular mass, or assign oxidation states, or recognise a Lewis acid – so we look for opportunities to ask students to rehearse and apply this knowledge in contexts that arise in later teaching. At the end of a previous lesson everyone seemed to understand the difference between respiration and breathing – but it sensible to find opportunity for them to rehearse the distinction. 2

There is then a level of structure due to linkages back and forth between the components of the teaching sequence.

So where the 'primary structure' is necessary to build up knowledge in a logical way in order that the teaching scheme functions to provide a coherent learning experience (teaching makes sense at the time), and the secondary structure allows progression toward more sophisticated accounts and models as students develop, the 'tertiary structure' offers reinforcement of learning to ensure the course functions as an effective long term learning experience (that what was taught is not just understood at the time, but is retained, and readily brought to mind in relevant contexts, and can be applied, over the longer term).

Quaternary structure – locating the course in the wider curriculum experience

What about quaternary structure? Well, commonly a student is not just attending one class or lecture course. Their curriculum consists of several different strands of teaching experiences. At upper secondary school level, for example, the learner may attend chemistry classes interspersed with physics classes, biology classes and mathematics classes. Their experience of the curriculum encompasses these different strands. Likely, there are both salient and other less obvious potential linkages between these different courses. Conservation of energy from physics applies in chemistry and biology. Enzymes are catalysts, so the characteristics of catalysts apply to them. The nature of hydrogen bonds may be taught in chemistry – and applied in biology. In that case, it would be useful for the learners if the topic was taught that concept in the chemistry class before it was needed in biology.

And just as there may be aspects of logical sequencing of ideas across the strands to be considered, there may be other potential links where the teacher in one subject can draw upon, exemplify, or provide opportunities to review, what has been taught in the other.

Level of structureFeature of sequencing
primary structurelogical sequencing of concepts to identify and later build on prerequisites
secondary structurespiral curriculum to build up sophistication of understanding
tertiary structurecross-linking between lessons along strand to reinforce learning by finding opportunities to revisit, review, and apply prior learning
quaternary structurecross links between courses to build up integrated (inter-*)disciplinary knowledge
levels of structure in well-designed curriculum

(* in a degree course this may be coordinating different lecture courses within a discipline; in a school context this may be relating different curriculum subjects)

Afterword

How seriously do I intend this comparison? Of course this is just an analogy. It is easy to see that it does not hold up to detailed analysis – there are more ways that curricular structure is quite unlike protein structure, and the kinds of units and links being discussed in the two cases are of very different nature.

Is there any value in such a comparison if the analogy is somewhat shallow? Well, devices such as analogies operate as thinking tools. Most commonly we use teaching analogies to help 'make the unfamiliar familiar' by showing how something unfamiliar is somewhat like something familiar. This can be a useful first stage in helping someone understand some new phenomena or concept.

In teaching science we commonly make analogies with everyday phenomena to help introduce abstract science concepts. Here I am using a scientific concept (protein structure) as the analogue for the target idea about sequencing teaching.

Read about scientific analogies

My motivation here was to prompt teachers (and others who might read the book when it is finished) who are already familiar with general ideas about curriculum and schemes of work to think about a parallel (albeit, perhaps a somewhat forced one?) with something rather different but likely already very familiar – protein structure. Chemists and science teachers are likely to already appreciate the different levels of structure in proteins, and how the different aspects of the nature of polypeptide chains and the links formed between amino acid residues inform the overall shape, and therefore the functionality, of the structure.

Perhaps this thinking tool will entice readers to think about how conceptual links within and between courses of study can support the functionality of teaching? Perhaps they will dismiss the comparison, pointing out various ways in which the level of structure in a well-planned curriculum are quite different from the levels of structure in a protein. Of course, if they can do that insightfully, I might suspect that this 'teaching analogy' will have done its job.

Work cited:
Note:

1 Sometimes the term polyamide is reserved for synthetic compounds and contrasted with polypeptides as natural products.

2 This can be useful even when students 'seem' to have grasped key ideas. When they remember that 'everything is made of atoms' we may not appreciate they think that implies chemical bonds contain atoms. When they seem to have understood that cellular metabolism depends upon respiration, we may not appreciate they think that this does not apply to plants when the sun is shining.

The heart-stopping queen

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'.

An article in October's Chemistry World

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).

Posting at Justin Brower's blog

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.

Two views of a voltage-gated sodium channel. (Source: Protein Data Bank). The second view shows the protein located in the membrane (represented in grey).

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.

The same protein molecule, showing sites where two different toxins (shown as green and yellow) are known to bind and change the conformation of the structure preventing the 'gate' functioning. (Source: Protein Data Bank).

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).

Individual heart cells beat in this YouTube video from Wake Forest Baptist Medical Center's Institute for Regenerative Medicine

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 science analogies

Read about making the unfamiliar familiar

target: sodium channels in cell membraneanalogue: internal combustion engine valves
positive mappingpoison may stop channels closingvalves may stick in open position
cell does not function with channels unable to closeengine does not function with valves stuck open
if nerve and heart cells do not function, paralysis occurs, and person diesif engine does not work, car does not go
negative mappingtissue damage will soon be irreversiblevalves may sometimes be freed up, restoring engine function – a quick response is not critical
Mapping between target idea and analogue
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