enzymes - Science-Education-Research

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.

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:

Carlsen, L. (2019). After Salisbury Nerve Agents Revisited. Molecular Informatics, 38(8-9), 1800106. doi:https://doi.org/10.1002/minf.201800106
Kammer, M., Kussrow, A., Carter, M. D., Isenberg, S. L., Johnson, R. C., Batchelor, R. H., . . . Bornhop, D. J. (2019). Rapid quantification of two chemical nerve agent metabolites in serum. Biosensors and Bioelectronics, 131, 119-127. doi:https://doi.org/10.1016/j.bios.2019.01.056
Nepovimova, E., & Kuca, K. (2018). Chemical warfare agent NOVICHOK – mini-review of available data. Food and Chemical Toxicology, 121, 343-350. doi:https://doi.org/10.1016/j.fct.2018.09.015
Pita, R., & Domingo, J. (2014). The Use of Chemical Weapons in the Syrian Conflict. Toxics, 2(3), 391-402.
Taber, K. S. (2019). The Nature of the Chemical Concept: Constructing chemical knowledge in teaching and learning. Cambridge: Royal Society of Chemistry.

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.

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 structure	Feature of sequencing
primary structure	logical sequencing of concepts to identify and later build on prerequisites
secondary structure	spiral curriculum to build up sophistication of understanding
tertiary structure	cross-linking between lessons along strand to reinforce learning by finding opportunities to revisit, review, and apply prior learning
quaternary structure	cross 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:

Bruner, J. S. (1960). The Process of Education. New York: Vintage Books.
Taber, K. S. (2021). Squaring the circle: Circumnavigating an ontological tension between practical learning progression models and the complex, multi-facetted, and meandering nature of conceptual learning. In M. N. Bowman (Ed.), Topics in Science Education (pp. 1-100). New York: Nova Science Publishers Inc.

Note:

¹Sometimes 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.

Catalysis as an analogy for scaffolding

Keith S. Taber

Image by Gerd Altmann from Pixabay

A key part of teaching or communicating science, is about 'making the unfamiliar familiar'.

(Read about 'Making the unfamiliar familiar')

Analogies can be used as pedagogic devices to make the unfamiliar familiar' – that is by suggesting that something (the unfamiliar thing being explained) is somehow like something else (that is already familiar), the unfamiliar can start to become familiar. The analogy functions like a bridge between the known and the unknown. (Note: the idea of a bridge is being used as simile there – another device that can be used to help make the unfamiliar familiar.)

(Read about 'analogies in science')

(Read about 'similes in science')

For an analogy (or simile) to work, the person being taught or communicated with has to already be familiar with the 'source' that act as an analogue for the 'target' being communicated. (If someone did not know what a bridge was, what it is used for, then it would be no help to them to be told that an analogy can function like one! Indeed it would probably just confuse matters.)

An analogy is based on some mapping of structure between two different systems. For example, at one time a common teaching analogy was that the atom was like a tiny solar system. For that to be useful to a learner, they would need to be more familiar with the solar system than the atom. To be used as an effective teaching analogy, the learner would have to understand the relevant parts of the conceptual structure of the solar system idea that were being mapped across to the atom (perhaps a relatively large central mass, the idea of a number of less massive bodies orbiting in some way, a force between the central and peripheral bodies responsible for the centripetal acceleration of the orbiting bodies…).

A person might easily map across irrelevant aspects of the source to the target, perhaps as all the planets are different then all electrons must be different! This might explain why some students assume the force holding the atom together is gravitational!

(Read about 'Understanding Analogous Atomic and Solar Systems')

In teaching science, it is common to use everyday sources as analogues for scientific ideas. But, of course, it is also possible to use scientific ideas as the source to try to explain other target ideas.

Below I reproduce an extract from a recent publication (Taber & Li, 2001). I developed an analogy between enzymatic catalysis (a scientific concept) and scaffolding of learning (an educational or psychological concept), to use is a chapter I co-wrote with Xinyue Li .

(Read about 'Scaffolding learning')

The mapping I had in mind was something like this:

Aspect	Source (Enzymatic catalysis)	Target (Scaffolding)
Process	Chemical reaction	Development of new knowledge/skills
Impediment	Large activation energy – barrier far greater than energy available to reactant species	Large learning demand – gap between current capability and mastery of new knowledge/skill exceeds manageable 'learning quantum'
Intervention	Addition of enzyme	Mediation by 'teacher'
Mechanism	Provides alternative reaction pathway with small energy barriers	Structures learning by modelling activity, and leads learner through small manageable steps
Matching	The enzyme 'fits' the reactant molecule and readily binds	A good scaffold matches the learners' current capacity to progress in learning (in the so-called 'ZPD')
Degrees of freedom	The binding of the enzyme to a substrate 'guides' the subsequent molecular reconfiguration	The scaffolding guides the steps in the learning process taken by the learner

Mapping between two analogous conceptual structures

Scaffolding Learning as Akin to Enzymatic Catalysis

"Metaphors and analogies should always be considered critically, as the aspects that do not map onto the target they are being used to illustrate can often be as salient and as relevant as the aspects that map positively. Given that, and in the spirit of offering a way to imagine scaffolding (rather than an objective description) we suggest it may be useful to think of scaffolding learning as like the enzymatic catalysis of a chemical process in the body (see Figure 3).

Figure 3. Scaffolding learning can be seen as analogous to enzymatic catalysis (b) which facilitates a reaction with a substantive energy barrier (a).

Some chemical reactions are energetically viable (in chemical terms, exothermic) and so in thermodynamic terms, occur spontaneously. However, sometimes even theoretically viable (so spontaneous) reactions occur at such a slow rate that for all practical purposes there is no reaction. For example, imagine a wooden dining table in a room at 293 K (20˚C) with an atmosphere containing about 21% oxygen – a situation found in many people's homes. The combustion of the table is a viable chemical process ^[1] and indeed the wood will (theoretically) spontaneously burn in the air. Yet, of course, that does not actually happen. Despite being a thermodynamically viable process, the rate is so slow that an observer would die of old age long before seeing the table burst into flames, unless some external agent actively initiated the process. If parents returned home from an evening out to be told by their teenage children that the smouldering dining table caught alight spontaneously, the parents would be advised to suspect that actually this was not strictly true. Although the process would be energetically favourable, there is a large energy barrier to its initiation (cf. Figure 3, top image). Should sufficient energy be provided to ignite the table, then it is likely to continue to burn vigorously, but without such 'initiation energy' it would be inert.

The process of catalysis allows reactions which are energetically favourable, but which would normally occur at a slow or even negligible (and in the case of our wooden table, effectively zero) rate to occur much more quickly – by offering a new reaction pathway that has a much lower energy barrier (such that this is more readily breached by the normal distribution of particles at the ambient temperature).

In living organisms, a class of catalysts known as enzymes, catalyse reactions. Enzymes tend to be specific to particular reactions and very effective catalysts, so reactions akin to the burning of organic materials (as found in our wooden table) can occur as part of metabolism at body temperature. The second image in Figure 3 represents the same chemical reaction as in the top image (note the same start and finish points) reflecting how an enzyme changes the reaction pathway, but not the overall reaction. Two particular features of this graphical metaphor are that the overall process is broken down into a number of discrete steps, and the 'initiation energy' needed to get the process underway is very much smaller.

This is similar to the mediation of learning trough scaffolding, where a task that is currently beyond the capacity of the learner is broken down into a sequence of smaller steps, more manageable 'learning quanta', and the learner is guided along a learning pathway. The parallels go beyond this. Part of the way that an enzyme functions is that the enzyme molecule's shape is extremely well matched to bind to a target reactant molecule (something reflected in the teaching analogy of the 'lock and key' mechanism of enzymatic action: the enzyme and substrate molecules are said to fit together like a lock and key). This is analogous to how effective scaffolding requires a teacher to design a scaffold that fits the learner's current level of development: that is, her current thinking and skills. Once the substrate molecule is bound to the enzyme molecule, this then triggers a specific reconfiguration: just as a good scaffolding tool suggests to the learner a particular perspective on the subject matter.

Moreover, whereas a free substrate molecule could potentially follow a good many different pathways, once it is bound to the enzyme molecule its 'degrees of freedom' are reduced, so there are then significant constraints on which potential changes are still viable. Most organic chemistry carried out in vitro (in laboratory glassware) is inefficient as there are often many 'side reactions' that lead to unintended products, just as students may readily take away very different interpretations from the same teaching, so the yield of desired product can be low. However in vivo reactions (in living cells), being enzyme-catalysed, tend to give high yields.

The process of enzymatic catalysis therefore makes the preferred pathway much 'easier', offers a guide along the intended route, and channels change to rule out alternative pathways. Digital tools that support teaching to meet curricular aims, such as apps intended to be used by learners to support study, therefore need to offer similar affordances (structuring student learning) and constraints (reducing the degrees of freedom to go 'off track'). Clearly this will rely on design features built into the tool. Here we very briefly discuss two examples."

^[1] We avoid the term 'reaction' here, as strictly a chemical reaction occurs between specific substances. Wood is a material composed of a wide range of different compounds, and so the combustion of wood is a process encompassing a medley of concurrent reactions.
(Taber & Li, 2001, pp.55-58)

Work cited:

Taber, K. S., & Li, X. (2021). The vicarious and the virtual: A Vygotskian perspective on digital learning resources as tools for scaffolding conceptual development. In A. M. Columbus (Ed.), Advances in Psychology Research (Vol. 143, pp. 1-72). New York: Nova. (Download the chapter by clicking this link.)

Not me, I'm just an ugly chemist

Keith S. Taber

Actress **Francesca Tu** playing an 'ugly chemist', apparently.

The 1969 film 'The Chairman' (apparently released in the UK as 'The Most Dangerous Man in the World') was just shown on the TV. I had not seen it before, but when I noticed it was on I vaguely recalled having heard something about it suggesting it was a film worth watching, so thought I would give it a try. And it had "that nice Gregory Peck" in it, which I seem to recall was the justification given for one of my late wife's sweet little Aunties going to see 'The Omen' (wasn't that also about the The Most Dangerous Man in the World?).

Nobel prize winner AND man of action

Dr John Hathaway (played by Gregory Peck): scientist and international man of mystery

Peck plays a Nobel laureate chemist, so I got interested. He had received a letter from a Chinese scientist, an old mentor who had worked with him at Princeton, warning him not to go to visit him in China, which (a) piqued his interest as (i) he had had no contact with the colleague for a decade, and (ii) he had no plans to go to China, and (b) told us viewers he would be off to China.

Peck's character, Hathaway, is an American who is currently a visiting professor at the University of in London. He contacts his embassy, suspecting there must be something of international significance in the message.

Hathaway's love interest (played by Anne Heywood) is seen teaching in the biophysics department

It transpires that this Nobel prize winning chemist had some kind of background in "the game" – intelligence work (of course! Well, at least this gets away from the stuffy stereotype of the scientist who never leaves the lab.), but had reached an epiphany three years earlier when his wife had been killed in a road accident while he was driving, and the experience of being with her as she died had led to him deciding that every life was unique and precious (as he later explained to Mao Zedong, the eponymous Chairman of the title) and he would no longer take on a job that would oblige him to kill. (Later in the film Hathaway seemed to have forgotten his high principles when he accepted a pistol as he made an escape in a stolen armoured car.) The intelligence communities had become aware that China had identified a natural product that could be extracted in tiny quantities, an enzyme which allowed any crop to be grown under any conditions.

The film seemed to be intended to make some serious points about detente, the cold war, the cultural revolution and the cult of Mao, and political and moral imperatives.

It is the responsibility of all to cultivate themselves, and study Marxism-Leninism deeply. / [Thinks: Sure, as soon as we've finished cultivating this rice.]

The allies argue that China will keep the new discovery to itself and use it to bring developing countries with food shortages into its sphere of influence, and Hathaway seems motivated to ensure all of humanity should share the benefits, thus he accepts the mission to go to China; later Mao agrees to provide a written promise that if Hathaway helps in the research then he can leave China at any time he likes and take with him whatever information he wishes to share with the world.

For the rest of the film to make any sense, Hathaway and the viewer have to assume that the promise and document will not be honoured (and it seems to be assumed that a character simply suggesting this is all Hathaway, or indeed any of us, need to be convinced of this). Yet, (SPOILER ALERT) when Hathaway is safely back in London, and has decoded the structure, he is told that the Western authorities have decided not to share the discovery.

I was not sure what a young audience who do not remember the context might make of some aspects of the film. We are told that the operation to obtain the enzyme, operation Minotaur *, has according to the US officer in charge cost half a billion federal dollars (which seems a lot for 1969, even allowing for some exaggeration) and was supported by the UK with a contribution a British intelligent officer suggests was likely "two pounds ten" (i.e., £2.50).

I wondered whether Chinese agents actually operated so easily in moving into and out of Hong Kong as is suggested, and there was some interesting brief news footage playing on a hotel television suggesting (British) Hong Kong police were responding to civil unrest in a way that does not seem so different from contemporary reports under the already notorious 2020 Hong Kong national security law.

Anyway, I will try and avoid too many plot spoilers, but suffice to say I was interested and intrigued in how matters would pan out for the first three quarters of the film (until people started firing guns and throwing grenades, at which point I lost any investment I'd had in what would happen.)

Science in the media in 1969

The science in the film was far-fetched, but perhaps not too far fetched for a general audience in 1969. 1969 was after all, a different age. (In 1969 the Beatles were still together, 'In the Court of the Crimson King' was released, and NASA's landing on the moon showed just what the USA could achieve when a President believed in, and encouraged, and resourced, the work of scientists and engineers.)

A transmitter made of undetectable plastic parts, suppposedly

Hathaway was bugged (through a sinus implant) such that his US /UK handlers (and USSR observer) could hear everything he said and everything said to him from half a world away through a bespoke satellite that the Chinese had not noticed recently appearing over their territory. The Americans initially had serious trouble with signal:noise and just made out the odd consonant, and so could not understand any speech, but a UK intelligence officer suggested simply filling in the gaps with uniform white noise, which, amazingly, and (even more amazingly) immediately at first attempt, gave a much cleaner sound than I can get on FaceTime or Zoom or Skype today (Implied message: the British may be the poor relatives, but have the best ideas?)

High stakes communication

What Hathaway did not know (but perhaps he should have been paying more attention when he was told the implanted transmitter was a 'remedy' in case the Chinese would not let him leave the country?) was that the implanted transmitter also had an explosive device that could be used if he needed to be terminated.

Indeed there was supposedly enough plastic explosive that when Hathaway was invited to meet Chairman Mao (was he meant to be 'the most dangerous man in the world'?) it raised the issue of whether the device should be used to remove the Chairman as he played table tennis with Hathaway (asking us to believe that democratic governments might sanction the violent summary execution of perceived enemies, without due legal process, in foreign lands) *.

Is it stretching credibility to believe that democratic governments would sanction the violent summary execution of perceived enemies, without due legal process, on foreign soil?

The command code to explode the device was stored on magnetic tape that took over thirty seconds to execute the instructions (something that seems ridiculous even for 1969, and was presumably only necessary to provide faux tension at the point where the clock counts down and the audience are supposed to wonder if the British and Americans are going to have to kill the film's star off before the movie is over).

Equally ridiculous, the implant supposedly had the same density as human tissue so that it would not show up on X-rays. (A wise precaution: when in Hong Kong, Hathaway is lured to some kind of decadent, Western, casino-cum-brothel where Chinese agents manage to covertly X-ray him from the next room as he enjoys a bowl of plain rice with a Chinese intelligence officer – quite a technical feat).

Of course, human tissue is not all of one 'density' (in the sense of opaqueness to X-rays), or else there would be little point in using X-rays in medical diagnosis – actually a sinus should show up on an X-ray as an empty cavity!

Highly technical information appeared on screens at the listening post as displays little more complex than sine waves – not even the Lissajous figures so popular with 1970s sci-fi programmes.

At one point Hathaway broke into a room through a thick solid metal floor by using just a few millilitres of nitrohydrochloride acid (aqua regia) that was apparently a standard bench reagent in the Chinese biochemistry laboratory (these enzymes must be pretty robust, or perhaps Professor Soong had a side project that involved dissolving gold), and which Hathaway was quite happy to carry with him in a small glass bottle in his jacket pocket. The RSC's Education in Chemistry magazine warns us that "because its components are so volatile, [aqua regia] is usually only mixed immediately prior to use". Risk assessment has come on a lot since Dr Hathaway earned his Nobel.

Laboratory safety glasses: check. Bench mat: check. Gloves: check. Lab coat: check. Fume cupboard: check.

The focal enzyme was initially handled rather well – the molecular models looked convincing enough, and the technical problem of scaling up by synthesising it seemed realistic. The Chinese scientist could not produce the enzyme in quantity and hoped Hathaway could help with the synthesis – a comparison was made with how producing insulin originally involved the sacrifice of many animals to produce modest amounts, but now could be readily made at scale. I seem to recall from my natural products chemistry that before synthetic routes were available, sex hormones were obtained by collecting vast amounts of 'material' from slaughterhouses and painstakingly abstracting tiny quantities – think the Curies, but working with with tonnes of gonads rather than tonnes of pitchblende.

Before Hathaway had set out on his mission he had pointed out that the complexity of an enzyme molecule was such that he could never memorise the molecular structure as it would contain anything from 3000 to 400 000 atoms. So, the plot rather fell apart at the end (SPOILER ALERT) as he brings back a copy of Mao's little red book, in which his mentor had hidden the vital information – as the codes for three amino acids.

Ser – Tyr – Pro

Hm.

Beauty and the chemist

You are beautiful, just like your mother – but OBVIOUSLY not as clever as your dad.

But, what sparked me to wrote something about this film, was some dialogue which brought home to me just how long ago 1969 was (I was still in short trousers – well, to be honest, for about half the year I am still in short trousers, but then it was all year round). Hathaway is flown to China from Hong Kong, and on arrival is met by the daughter of his old mentor:

Soong Chu (Francesca Tu): I am Professor Soong's daughter

Dr. John Hathaway (Peck): You look a great deal like your beautiful mother.

Soong Chu: Not I. I am just an ugly chemist

Hathaway: I read your recent paper on peptides. I thought it was brilliant – for a woman.

Soong Chu: Oh, I agree, but my father helped a great deal.

Working in the dark to avoid any more comments on her looks?

I was taken aback by the reference to just being an ugly chemist, and had to go back and check that I'd heard that correctly. Was the implication that one could not be beautiful, and a chemist? Nothing more was said on the topic, but that seemed to be the implication. And what is meant by being 'just' a chemist?

Hathaway's comment that Soong Chu's paper had been brilliant, was followed by a pause. Then came "…for a woman". Did he really say that?

Not bad for a girl

I was waiting for the follow-up comment which would resolve this moment of tension. This surely had to be some kind of set up for a punch line: "It would have been beyond brilliant for a man", perhaps.

But no, Soong Chu just agreed. There did not seem to be intended to be any tension or controversy or social critique or irony or satire there. So much for Soong Chu's membership of the Red Guard and all the waving of the thoughts of the Chairman (she would have known that "Women represent a great productive force in China, and equality among the sexes is one of the goals of communism").

"The red armband is the most treasured prize in China…[representing] responsibility…[as] a leader of our revolution"

Soong Chu had needed the help of her father to prepare her paper, but he had presumably declined to be a co-author, not because his input did not amount to a substantial intellectual contribution (the ethics of authorship have also come on a bit since then), but because his daughter was a woman and so not able to stand on her own two feet as a scientist.

This dialogue is not followed up later in the film.

So, this is not planting a seed for something that will later turn out to be of significance for character development or plot, or that will be challenged by subsequent scenes. It is not later revealed that Soong Chu has a parallel career as Miss People's Republic of China (just as Hathaway is a chemist and also a kind of James Bond figure). Nor does it transpire that Professor Soong had been senile for many years and all of his work was actually being undertaken for him by his even more brilliant daughter.

Sadly, no, it just seems to be the kind of polite conversation that the screenwriters assumed would be entirely acceptable to an audience that was presumably well aware that females cannot be both beautiful and scientists; and that women need help from men if they are to be successful in science.

Times have changed … I hope.

* Interestingly, I've now found a poster for the film which seems to suggest that the whole purpose of the operation was not to acquire the enzyme structure at all, but to get Hathaway close enough to Mao to assassinate him.

Getting viewers to watch the film under false pretences

This seems to describe a very different cut to one I watched – where the audience with Mao seems to have surprised everyone, and the senior intelligence officers contacted their governments to alert them of this unexpected opportunity!