an autodidact meets a dilettante…

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A DNA dialogue 2: the double helix

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Canto: Ok we talked about base pairs at the end of dialogue 1. A (nucleo)base pair is, duh, a pairing of nucleobases. There are four types of base in DNA – adenine and thymine, which always pair together, and the other pairing, cytosine and guanine.

Jacinta: Please explain – what’s a nucleobase, what do they do, and why do they come in pairs?

Canto: Well, let’s see, how do we begin… DNA stands for deoxyribonucleic acid…

Jacinta: So it’s an acid. But bases are like the opposite of acids aren’t they? So how can an acid be constructed of its opposite?

Canto: Look, I can’t answer that right now – I haven’t a clue – but let’s keep investigating the structure and function, and the answers might come. So, you’ll know that there was a battle in the 1950s to elucidate the structure of DNA, and it was found to form a double helix two strands of – I don’t know what – connected to each other in a twisted sort of way by, I think, those base pairs connected by hydrogen bonds. Anyway, here’s a fairly typical explanation, from Nature Education, which we’ll try to make sense of:

The double helix describes the appearance of double-stranded DNA, which is composed of two linear strands that run opposite to each other, or anti-parallel, and twist together. Each DNA strand within the double helix is a long, linear molecule made of smaller units called nucleotides that form a chain. The chemical backbones of the double helix are made up of sugar and phosphate molecules that are connected by chemical bonds, known as sugar-phosphate backbones. The two helical strands are connected through interactions between pairs of nucleotides, also called base pairs. Two types of base pairing occur: nucleotide A pairs with T, and nucleotide C pairs with G.

Jacinta: So I think I have a problem with this description. I think I need a picture, fully labelled. So the two strands themselves are made up of nucleotides, and the connections between them are made up of bonded sugar and phosphate molecules? But the strands are connected, via sugar and phosphate, in particular ways – ‘through interactions’ – which only allow A to pair with T, and C to pair with G?.

Canto: I think that’s right. Maybe we can find a picture.

Jacinta: Ok, so we got it completely wrong. The backbone, of sugar-phosphate, is the outer, twisted strand, or two of them, like the vertical bars of a twisted ladder, or the toprails of a spiral staircase, and the base pairs are like the stairs themselves, made of two separate parts, the bases, bonded together by hydrogen…

Canto: Forget the description, the picture above is worth all our words. It also tells us that the DNA molecule is around 2 nanometres wide. That’s two billionths of a metre. And 3.4 nanometres long for a full twist of the double helix, I think.

Jacinta: Whateva. There’s also this claim that the two strands are ‘anti-parallel’. It looks to me as if they’re simply parallel, but twisted. What does this mean? Is it significant?

Canto: I don’t know – maybe we’ll find out next time. I’m already exhausted.

Jacinta: …….

Written by stewart henderson

January 16, 2020 at 5:13 pm

Posted in biochemistry, DNA, science

Tagged with , ,

thoughts on smoking, cancer and government

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a simple and provenly effective solution

Recently I was talking about unhealthy habits to my students – I teach academic English to NESB students – and smoking came up. A student from Saudi Arabia piped up: ‘smoking isn’t unhealthy’.
Now, considering that this same student, a married man aged around thirty, had previously told me that, in ancient times, humans lived to be over 900 years old – ‘it says so in the Bible’ – I wasn’t entirely surprised, and didn’t waste too much time in arguing the point. Actually, I think now he probably mentioned the Bible to show or suggest that Moslems and Judeo-Christians might agree on some things!

Of course, this student was a smoker. Many of my male students are. These students are predominantly Chinese, Vietnamese and Arabic speakers, that’s to say from countries whose governments have acted less forcefully in dealing with smoking than has the Australian government. I myself smoked. albeit lightly, until the age of 24 (a long time ago). Now, having been diagnosed with bronchiectasis, I’m extremely intolerant of cigarette smoke, not to say smokers.

I’m currently ploughing though Siddhartha Mukherjee’s classic Emperor of All Maladies, and have just finished the section on smoking and cancer, and the battle with tobacco companies in libertarianism’s heartland, the USA. 

Cigarette smoke contains a number of carcinogens – but what is a carcinogen? It’s basically a product or agent that has a reasonable likelihood of causing cancer, which doesn’t of course mean that it will cause cancer in every instance. You can play Russian roulette with the 60 or more well-established carcinogens in cigarette smoke, and risk-taking young men in particular will continue to do so, but it’s a massive risk, and the dangers increase with age and length and frequency of use. Lung cancer is the most regularly cited outcome, but as the US surgeon-general’s 2010 report shows in vast detail, cancers of the larynx, oral cavity, pharynx, oesophagus, pancreas, bladder, kidney, cervix, stomach and liver can all be induced by this inhaled chemical cocktail. And cancer isn’t the only issue. There is the problem of nicotine addiction, as well as cardiovascular and pulmonary disease, and fertility and foetal developmental effects. 

With all this evidence, why do people still smoke, and why don’t governments step in? Drugs with far less devastating effects are illegal, so what gives?

Of course the role governments should play in determining or influencing public health has always been debated, as has the efficacy of banning particular substances and practices. The situation isn’t helped by the facts on the ground, an ad hoc regime in which relatively harmless substances such as marihuana are banned almost worldwide, while proven carcinogens like tobacco, costing millions in treatment, are merely ‘discouraged’ to varying degrees. Similarly, in some countries you have ‘cults’ like falun gong being treated as highly dangerous and criminal while more mainstream ‘cults’ such as christianity, no less or more nonsensical, being given a free ride. None of which promotes faith in government decision-making regarding our physical or psychological health.
Even so, I believe governments should play a role. We pay taxes to government so that it can organise our particular state more effectively for all of its citizens – and that means subsidising education, health and general welfare, to reduce inequalities of opportunity and outcome. Democratic government and an open society helps to reduce government ineptitude, ignorance and corruption. The science and technology sector in particular – a proudly elitist institution – should play a more significant role in government decision-making. But a real weakness of capitalist democracy is that political leaders are too often swayed by business leaders, and the money and influence they bring to the table, than by knowledge leaders. This obeisance paid to business success, with insufficient regard paid to scientific evidence, is possibly the greatest failing of modern political society.

Written by stewart henderson

January 5, 2020 at 10:47 am

How did we get language?

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a most persuasive hypothesis

                                          a most persuasive hypothesis

According to National Geographic there are, or were, at least 7000 languages globally. That was a few years ago and they say the numbers are dwindling, so who knows. There may also be a lumpers v splitters issue here – are they all unique languages or are some just variants of the same language?
There are organisations out there dedicated to preserving rare and endangered languages via recordings and analyses, but is this such a vital project? After all, when a language dies out it’s not because their speakers have gone dumb, it’s because they’ve died and their offspring are speaking one of the more common, viable languages of their region. And this of course raises the question of whether language diversity is a good in itself, in the way that species diversity is seen to be, or whether we’d be better off speaking fewer languages globally. It’s actually quite a dangerous topic, since language is very much a cultural artefact, and cultural suppression, often of the most brutal kind, is currently going on in various benighted parts of the world.

The diversity of language also raises another fascinating question – did it evolve once or many times? Was there an ‘ur-language’ or proto-language from which all these diverse languages sprung? Take for example, the Australian Aboriginal languages. Anthropologists claim that there were some 250 of them around when Europeans arrived with their much smaller number of languages. And Aborigines arrived here about 50,000 years ago. But how many, and with how many different languages? These are perhaps the unanswerable questions that Milan Kundera liked so much. However, linguists have been studying surviving Aboriginal languages intensively for some time, and are mostly agreed that they can be ‘lumped together’ in a small number of dispersed family groups with distinctive features, which suggests that, on arrival, the number of languages was much smaller.

Added to this evidence (if you can call this evidence), is the recent understanding that our species, Homo sapiens, spread out from the African continent in separate waves, from 250,000 years ago to 70,000 years ago. So it seems to me more likely that there was a proto-language, developed in Africa and moving out with one of those waves, and taking over the world, through breeding or cultural exchange, and diversifying with those migrations and their growing cultural diversity. Then again, maybe not.

We used to to describe the world before the emergence of writing as ‘prehistoric’, which seems rather arrogant now, and the word has fallen out of favour. And yet, there is some sense in it. Writing (and drawing) always tells us a story. It provides a record. That’s its intention. It’s the beginning of the modern story, and so, history, in a sense. All of what comes before writing, in the story of humans, is unrecorded, accidental. Scraps of stuff that require a lot of interpretive work. That’s what makes the development of writing such a monumental breakthrough in human affairs. It happened in at least three separate places, only a few thousand years ago. Human language itself, of course has a much longer history. But how much longer? Eighty thousand years? A hundred thousand? Twice that long? Currently, we haven’t a clue. The origin of language is regarded by many authorities as one of the toughest problems in science. It isn’t just a question of when, but of how, where and why. Good luck with answering that lot.

Written by stewart henderson

December 17, 2019 at 11:37 pm

how statins work 3: the beginnings of cholesterol, from Acetyl-CoA

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Coenzyme A – an acetyl group attaches to the -SH shown in red

So how is cholesterol made in the body? We need to know this in order to understand how statins inhibit or interfere with this process.

I’ve shown the actual structure of cholesterol in part 1 of this series, but remember it’s a sterol, which is a steroid – four carbon rings with hydrogen atoms attached – in which one of the hydrogens is replaced by an alcohol group. The particular form of sterol called cholesterol, with a 7-carbon chain attached to the end-carbon ring (the D ring), and three methyl groups attached to specific carbons in the rings and chain (it’s better to look at the skeletal structure in part 1). There are precisely 27 carbon atoms specifically placed within the molecule.

I’m using a set of videos to understand how cholesterol is synthesised – it might be best to look at them yourself, but I’m writing it all down to improve my own understanding. So we start by understanding something about acids and their conjugate bases. Apparently an acid is a molecule which is capable of donating protons into solution. Take pyruvic acid and its conjugate base pyruvate. Here’s what Wikipedia says about them:

Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO, is a key intermediate in several metabolic pathways throughout the cell.

I don’t understand the first sentence, but no matter, pyruvic acid is a 3-carbon molecule with a carboxylic acid at one end and a ketone group in the middle of the molecule (according to Britannica, a ketone is ‘any of a class of organic compounds characterized by the presence of a carbonyl group in which the carbon atom is covalently bonded to an oxygen atom. The remaining two bonds are to other carbon atoms or hydrocarbon radicals)’. The proton that comes off the oxygen of the alcohol group of the pyruvic acid can be donated into the surrounding solution, increasing its acidity. The pyruvic acid is thus transformed into its negatively charged conjugate base (it’s no longer capable of donating protons but it can receive them). This is the case with all acids in the cytoplasm of cells. As inferred in the quote above, conjugate bases are vital components of biosynthetic pathways. Most of the molecules in the cytoplasm will exist as pyruvate at a physiological pH of around 7.5.

Next – and hopefully this will become clear eventually – we’re going to look at two molecules, NAD+ (nicotinamide adenine dinucleotide) and NADP+ (nicotinamide adenine dinucleotide phosphate). They transport electrons, and are capable of accepting a hydride anion, which is a hydrogen atom with a negative charge. The normal hydrogen atom, called protium, has a proton and an electron only. When it donates away its electron it becomes a hydrogen cation, and when it gains an electron it becomes a hydride anion.

NAD+ is an adenine organic base bound to a ribose sugar. Then there are two phosphate groups coming off the ribose sugar, the second of which attaches to another ribose sugar. This second ribose sugar has nicotinamide attached to it (see below),

in which the phosphate groups are magenta-coloured circles. To explain something about ribose sugars, here’s something from Pearson Education:

The 5-carbon sugars ribose and deoxyribose are important components of nucleotides, and are found in RNA and DNA, respectively. The sugars found in nucleic acids are pentose sugars; a pentose sugar has five carbon atoms. A combination of a base and a sugar is called a nucleoside. Ribose, found in RNA, is a “normal” sugar, with one oxygen atom attached to each carbon atom. Deoxyribose, found in DNA, is a modified sugar, lacking one oxygen atom (hence the name “deoxy”). This difference of one oxygen atom is important for the enzymes that recognize DNA and RNA, because it allows these two molecules to be easily distinguished inside organisms.

So, just for my own understanding, nucleotides include phosphate groups. NAD+ is a dinucleotide, with two nucleotides (ribose sugars with phosphate groups attached), attached to adenine and to nicotinamide molecules. Also, NAD+ has a positive charge around the nicotinamide – on its nitrogen atom.

NAD+ becomes neutralised by accepting a hydride anion (one proton and two electrons) and becomes NADH, or reduced NAD. Now, remembering NADP+, it has an extra phosphate group on the ribose sugar of the adenine nucleotide (also called an organic base, apparently). Like NAD+, NADP+ can accept a hydride anion (becoming reduced NADP) and then later exchange it in another reaction. Effectively these molecules are electron carriers, collecting electrons and transporting them to where they’re needed for other reactions.

Now to introduce something else completely new for me – Acetyl-CoA (acetyl coenzyme A). A quick grab again, this time from Wikipedia:

Acetyl-CoA is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid [Krebs] cycle to be oxidized for energy production

Acetyl-CoA is found, and presumably produced, in mitochondria, and as part of this cholesterol-synthesising pathway it needs to be removed from the ‘mitochondrial matrix’. What’s that, I ask. So here’s a bit about the mitochondrial matrix, from yet another source, this time Study.com:

The mitochondrion consists of an outer membrane, an inner membrane, and a gel-like material called the matrix. This matrix is more viscous than the cell’s cytoplasm as it contains less water. The mitochondrial matrix has several functions.It is where the citric acid cycle takes place. This is an important step in cellular respiration, which produces energy molecules called ATP. It contains the mitochondrial DNA in a structure called a nucleoid. A mitochondrion contains its own DNA and reproduces on its own schedule, apart from the host cell’s cell cycle. It contains ribosomes that produce proteins used by the mitochondrion. It contains granules of ions that appear to be involved in the ionic balance of the mitochondrion.

So basically this matrix is like (or equivalent to) the cell’s cytoplasm, only more viscous, and contains ribosomes, one or more nucleoids and ionic granules, inter alia.

Acetyl-CoA is essential to the biosynthesis of cholesterol, and is found initially in the mitochondrial matrix, and we need to look at the pathway for its removal from that matrix into the cytoplasm, where all the action occurs.

Intruding into the mitochondrial matrix from the (quite impermeable) inner cell membrane are the cristae, which give the membrane more of a surface layer for interactions. This inner membrane is the site of oxidative phosphorylation. What’s that, I ask. Well, it’s key to the production of ATP, and at least I know that ATP is the ‘energy molecule’, and that it’s produced in mitochondria. Here’s something about the process from Khan Academy:

Oxidative phosphorylation is made up of two closely connected components: the electron transport chain and chemiosmosis. In the electron transport chain, electrons are passed from one molecule to another, and energy released in these electron transfers is used to form an electrochemical gradient. In chemiosmosis, the energy stored in the gradient is used to make ATP.

So a strong proton gradient is built up across the inner membrane of the mitochondrion. It’s a concentration gradient but also an ‘electrical potential difference’ gradient, so that the electrical potential within the matrix is lower, by some 160 millivolts, than that across the inter-membrane space. The protons within this space are unable to pass back into the matrix. The only way they can get back into the matrix is by means of ATP synthase which can harness the energy from the protons as they move down the chemical and electrical gradient, and use that energy to bind ADP to inorganic phosphate to create ATP.

I don’t fully understand all that, but the main point here is that the mitochondrial inner membrane is very ‘tight’, which makes it difficult to transfer Acetyl-CoA out of the matrix and into the inter-membrane space, from which it can more easily diffuse through the more permeable outer membrane into the cytoplasm.

The structure of Acetyl-CoA: it consists of an acetic acid molecule (CH3COOH) with a thioester link to the thiol group of a coenzyme A molecule. The importance for us here is this thiol (HS) group, which is similar structurally to an alcohol (HO) group, as sulphur has similar properties to its periodic table neighbour, oxygen. So thiol groups can be linked to carboxylic acid groups as alcohol groups can. Acetyl essentially means acetic acid with the alcohol removed. To get this Acetyl-CoA out of the matrix, it is first bound to oxaloacetate, a four-carbon molecule, to create citrate, the first molecule of the citric acid cycle. This citrate can be passed through the mitochondrial inner membrane and into the cytoplasm where it can be converted back into Acetyl-CoA.

So the conjugate base, oxaloacetate, has carboxylic acid groups, attached to the first and fourth carbon atoms, that have lost their protons into solution. An enzyme within the matrix is able to combine oxaloacetate with Acetyl-CoA and water to create citrate…

Okay, this is proving to be a much longer story than I might’ve hoped, but I like to be thorough – and in reality I’m still not being thorough enough. There’s a lot of rubbish on the internet about statins, much of it self-serving in one way or another, so I’ll just keep plodding along until I feel at least halfway informed about the matter. Meanwhile, you just keep getting on with your work, and don’t mind me.

References

Cholesterol biosynthesis part 1, by Ben1994, 2015

Cholesterol biosynthesis part 2, by Ben 1994, 2015

https://www.britannica.com/science/ketone

http://www.phschool.com/science/biology_place/biocoach/bioprop/ribose.html

https://en.wikipedia.org/wiki/Acetyl-CoA

https://study.com/academy/lesson/mitochondrial-matrix-definition-function-quiz.html

https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/oxidative-phosphorylation/a/oxidative-phosphorylation-etc

Written by stewart henderson

October 14, 2019 at 5:26 pm

women of note 1: Mary Anning, palaeontologist

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She sells sea-shells on the sea-shore,
The shells she sells are sea-shells, I’m sure
For if she sells sea-shells on the sea-shore
Then I’m sure she sells sea-shore shells. 

Terry Sullivan, 1908 – said to be inspired by Mary Anning’s fossickings

Unfortunately, I want to write about everything.

So now I begin an occasional series about women to be celebrated and never forgotten.

Mary Anning was born in the seaside town of Lyme Regis, Devon, in 1799 and died there, too young, of breast cancer in 1847. According to Brian Ford, author of Too big to walk: the new science of dinosaurs, she was ‘the first full-time professional palaeontologist anywhere in the world’. It’s a fair statement; those before her were generalists, given the name ‘naturalists’, and made their livings as pastors or physicians, or were independently wealthy. The term ‘palaeontology’ was just starting to gain traction in the early nineteenth century, replacing the intriguing but probably short-lived ‘oryctology’, though fossil-finding and speculations thereon (mostly infused with religious or mystic beliefs) date back to civilisation’s dawn.

Fossil-hunting had become quite trendy from the late eighteenth century, and Mary’s dad, a cabinet-maker by trade, supplemented his income by selling fossil bits and pieces, discovered himself on the nearby cliffs, to locals and tourists (the region had become something of a haven for those escaping the Napoleonic wars). The cliffs around Lyme Regis on England’s south coast form part of the Blue Lias, alternating sediments of shale and limestone, very rich in fossils from the early Jurassic, around 200 mya.

Richard and Molly, Mary’s parents, had ten children, but only two, Joseph and Mary, survived infancy. Childhood diseases such as measles were often killers, especially among the poor – a reminder of how lucky we are to be living in an economically developed country in the 21st century. The Anning family was never well-off, and Richard died when Mary was just 11 years old. Mary herself just managed to escape death by lightning strike when she was a baby. The strike killed three women, one of whom was tending her at the time. But the family suffered many hardships besides infant mortality. Food shortages and rising prices led to riots in the neighbourhood, and Richard himself was involved in organising protests.

As kids, Joseph and Mary sometimes accompanied their father on fossil-hunting trips on the dangerous cliffs, which were subject to landslides. They would sell their finds, which were mostly of invertebrate fossils such as ammonite and belemnite shells, in front of their home, but clearly life would’ve been a real struggle in the years following Richard’s death, during which time they relied partly on charity. It wasn’t long, though, before Mary’s expertise in finding and identifying fossils and her anatomical know-how came to the attention of well-heeled fossickers in the region. In the early 1820s a professional collector, Thomas Birch, who’d come to know the family and to admire Mary’s skills in particular, decided to auction off his own collection to help support them. This further enhanced their reputation, and Mary became something of a local celebrity, reported on in the local papers:

This persevering female has for years gone daily in search of fossil remains of importance at every tide, for many miles under the hanging cliffs at Lyme, whose fallen masses are her immediate object, as they alone contain these valuable relics of a former world, which must be snatched at the moment of their fall, at the continual risk of being crushed by the half-suspended fragments they leave behind, or be left to be destroyed by the returning tide: – to her exertions we owe nearly all the fine specimens of ichthyosauri of the great collections.

Bristol Mirror, 1823 – quoted in Too big to walk, by Brian Ford, p61

As this article mentions, Mary Anning’s name is often associated with ichthyosaur fossils, but she also discovered the first plesiosaur, the identity of which was confirmed by Georges Cuvier – though he at first accused her of fraud. Amongst other contributions, she was the first to recognise that the conical ‘bezoar stones’ found around the cliffs of Lyme were in fact fossilised faeces of ichthyosaurs and plesiosaurs.

plesiosaur skeleton, beautifully sketched by Mary Anning

For my information, ichthyosaurs were marine reptiles dated from the early Triassic to the late Cretaceous periods (250-90 mya), though most abundant in the early period, after which they were superseded as the top marine predators by the plesiosaurs (approx 204-66 mya).

Anning’s exact contribution to palaeontology is impossible to determine, because so many of her finds were snapped up by professional collectors, in an era when attributions weren’t preserved with much care, and this would have been compounded by her status as an ‘uneducated’ amateur, and a woman. Contemporary commentary about her expertise was often infused with a subtle condescension. There’s little doubt that, had she been male, her admirers would have seen to it that her talents were sufficiently recompensed with scholarships, senior university posts, and membership of the prominent scientific societies. Instead, she remained a fixture at Lyme Regis – there’s no indication that she ever travelled, apart from at least one trip to London, though her expertise was recognised throughout Europe and America. It’s also likely that, coming from a family of Dissenters – a reformist Protestant group – she was regarded with suspicion by the Anglican-dominated scientific hierarchy of the time. Let’s take a look, for comparison, at some of the males she associated with, and who associated with her, and how their professional lives went:

Sir Henry de La Beche – KCB, FRS. That first TLA means ‘Knight Commander of the Bath’ or something similar. I seem to recall bestowing a similar title upon myself while commanding battleships in the bathtub at age six or so. Never received a stipend for it though. FRS means Fellow of the Royal Society of course. Son of a slave-owner who died young, Beche was brought up in Lyme Regis where he became a friend of Anning, sharing her interest in geological strata and what they contained. It’s not unlikely that she was an inspiration for him. He was able to join the male-only London Geological Society at age 21, and later became its President. He became a FRS in 1819 at the still tender age of 24. He was appointed director of the Geological Survey of Great Britain in the 1830s and later the first director of the Museum of Practical Geology in London (now part of the Natural History Museum). He was knighted for his genuine contributions to geology in 1848. Beche was in fact an excellent practical and skeptical scientist who gave support to Anning both financially and in his published work.

William Conybeare – FRS. Born into a family of ‘divines’ (at least on the male side) Conybeare became a vicar himself, and a typical clergyman-naturalist, with particular interests in palaeontology and geology. Educated at the elite (and all-male) Westminster School and at all-male Oxford University, after which he travelled widely through the country and on the Continent (all paid for by ‘a generous inheritance’) in pursuit of geological and palaeontological nourishment. He became an early member of the Geological Society, where he met and advised other notables such as Adam Sedgwick and William Buckland, and contributed papers, including one with Beche which summarised findings about ichthyosaurs and the possibility of another species among them, the plesiosaur. This was confirmed by Anning’s discovery and detailed description of a plesiosaur, which Conybeare later reported to the Geological Society, delighted to be proved correct. He failed to mention Anning’s name. In 1839 Conybeare, together with two other naturalist heavyweights, William Buckland and Richard Owen, joined Mary Anning for a fossil-hunting excursion. Unfortunately we have no smartphone recordings of that intriguing event.

William Buckland, DD [Doctor of Divinity], FRS. Born and raised in Devon, Buckland accompanied his clergyman dad on walks in the region where he collected fossil ammonite shells. He was educated at another elite institution, Winchester College, where he won a scholarship to Oxford. In 1813 he was appointed reader in minerology there, and gave popular lectures with emphasis on geology and palaeontology. He seemed to cultivate eccentricities, including doing field-work in his academic gown and attempting to eat his way though the animal kingdom. His most important association with Mary Anning was his coining of the term ‘coprolite’ based on Anning’s observation that these conical deposits, found in the abdomens of ichthyosaurs, were full of small skeletons. Clearly, Anning knew exactly what they were, but had no real opportunity to expatiate on them in a public forum. Women were often barred from attending meetings of these proliferating scientific societies even as guests, let alone presenting papers at them.

Gideon Mantell, MRCS [Member of the Royal College of Surgeons], FRS. Mantell was himself a rather tragic figure, whose association with Anning was less personal, though he did visit her once at her Lyme Regis shop. He was inspired more by news of her ichthyosaur discoveries, which reinforced an obsession with fossil hunting in his own region of Sussex, where many fossils of the lower Cretaceous were uncovered. Born in Lewes in Sussex, the fifth child of a shoemaker, he was barred from the local schools due to his family’s Methodism. He underwent a period of rather eccentric but obviously effective private tuition before becoming apprenticed to a local surgeon. Though worked very hard, he taught himself anatomy in his free time, and wrote a book on anatomy and the circulation of the blood. He travelled to London for more formal education and obtained a diploma from the Royal College of Surgeons in 1811. Returning to Lewes, he partnered with his former employer in treating victims of cholera, smallpox and typhoid epidemics, and delivering large quantities of babies, building up a thriving practice, but also somehow finding time for fossil-hunting, corresponding with others on fossils and geology, and writing his first paper on the fossils of the region. He started finding large and unusual bones and teeth, which turned out to be those of an Iguanadon, though it took a long time for this to be recognised, and he was mocked for his claims by experts such as William Buckland and Richard Owen. Although he was becoming recognised for his many writings and discoveries, he always remained something of an outsider to the establishment. He later fell on hard times and suffered a serious spinal injury from a horse-and-carriage accident, from which he never really recovered. He apparently died from an overdose of laudanum, used regularly as a pain-killer in those days.

Returning to Mary Anning, we see that class as well as sex was a barrier to intellectual acceptance in early nineteenth century Britain – but sex especially. Mary struggled on in Lyme Regis, recognised and sought out by other experts, but never given her full due. In the 1840s she was occasionally seen to be staggering about, as if drunk. In fact, she too was dosing herself on laudanum, due to the pain of advancing breast cancer. She died in 1847, aged 47.

I should point out that, though Mary Anning’s name is largely unknown to the general public, so are the male names mentioned in this article. We generally don’t fête our scientists very much, though they’re the ones that really change our world, and help us to understand it. Mary was helped out by luminaries such as Beche and Buckland in her later years, and received a small annuity from the British Association for the Advancement of Science. Upon her death, Beche wrote a modest eulogy, which he presented at a Geological Society meeting, which, had she been alive, Anning wouldn’t have been allowed to attend. It was later published in the transactions of the Society. Here’s how it begins:

 I cannot close this notice of our losses by death without adverting to that of one, who though not placed among even the easier classes of society, but one who had to earn her daily bread by her labour, yet contributed by her talents and untiring researches in no small degree to our knowledge of the great Enalio-Saurians [now known as Euryapsida], and other forms of organic life entombed in the vicinity of Lyme Regis ..

Mary Anning by her beloved cliffs, tool in hand, pointing to her not yet dead dog Tray, killed in the line of scientific duty…

References

https://en.wikipedia.org/wiki/Mary_Anning

https://ucmp.berkeley.edu/history/anning.html

https://www.nhm.ac.uk/discover/mary-anning-unsung-hero.html

https://www.britannica.com/biography/Mary-Anning

https://en.wikipedia.org/wiki/Ichthyosaur

https://en.wikipedia.org/wiki/Plesiosauria

https://www.bgs.ac.uk/discoveringGeology/time/Fossilfocus/ammonite.html

https://www.bgs.ac.uk/discoveringGeology/time/Fossilfocus/Belemnite.html

https://www.britannica.com/biography/Henry-Thomas-De-La-Beche

https://en.wikipedia.org/wiki/Henry_De_la_Beche

https://en.wikipedia.org/wiki/William_Conybeare_(geologist)

https://www.strangescience.net/conybeare.htm

https://en.wikipedia.org/wiki/William_Buckland

https://www.theguardian.com/science/2019/feb/03/gideon-mantell-play-fight-over-first-dinosaur

https://en.wikipedia.org/wiki/Gideon_Mantell

Written by stewart henderson

September 24, 2019 at 11:14 am

why do our pupils dilate when we’re thinking hard?

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Canto: So we’re reading Daniel Kahneman’s Thinking fast and slow, among other things, at the moment, and every page has stuff worth writing about and exploring further, it’s impossible to keep up.

Jacinta: Yes with this stuff it’s a case of reading slow and slower. Or writing about it faster and faster, unlikely in our case. A lot of it might be common knowledge, but not to us, though in these first fifty pages or so he’s getting into embodied cognition, which we’ve written about, but there’s new data here that I didn’t know about but which makes a lot of sense to me.

Canto: That’s because you’ve been primed to accept this stuff haha. But I want to focus here more narrowly on experiments Kahneman did early in his career with Jackson Beatty, who went on to become the leading figure in the study of ‘cognitive pupillometry’.

Jacinta: Presumably measuring pupils, which is easy enough, while measuring cognition or cognitive processes, no doubt a deal harder.

Canto: Kahneman tells the story of an article he read in Scientific American – a mag I regularly read in the eighties, so I felt all nostalgic reading this.

Jacinta: Why’d you stop reading it?

Canto: I don’t know – I had a hiatus, then I started reading New Scientist and Cosmos. I should get back to Scientific American. All three. Anyway, the article was by Eckhard Hess, whose wife noticed that his pupils dilated when he looked at lovely nature pictures. He started looking into the matter, and found that people are judged to be more attractive when their pupils are wider and that belladonna, which is used in cosmetics, also dilates the pupils. More importantly for Kahneman, he noted ‘the pupils are sensitive indicators of mental effort’. Kahneman was looking for a research project at the time, so he recruited Beatty to help him with some experiments.

Jacinta: And the result was that our pupils dilate very reliably, and quite significantly, when we’re faced with tough problem-solving tasks, like multiplying double-digit numbers – and they constrict again on completion, so reliably that the monitoring researcher can surprise the subject by saying ‘so you’ve got the answer now?’

Canto: Yes, the subjects were arranged so the researchers could view their eyes magnified on a screen. And of course this kind of research is easy enough to replicate, and has been. My question, though, is why does the pupil dilate in response to such an internal process as concentration? We think of pupils widening to let more light in at times of dim light, that makes intuitive sense, but – in order to seek a kind of metaphorical enlightenment? That’s fascinating.

Jacinta: Well I think you’re hitting on something there. Think of attention rather than concentration. I suspect that our pupils widen when we attend to something important or interesting. As Eckhard Hess’s wife noticed when he was looking at a beautiful scene. In the case of a mathematical or logical problem we’re attending to something intently as well, and the fact that it’s internal rather than external is not so essential. We’re looking at the problem, seeing the problem as we try to solve it.

Canto: Yes but again that’s a kind of metaphorical seeing, whereas your pupils don’t dilate metaphorically.

Jacinta: Yes but it’s likely that our pupils dilate in the dark only when we’re trying to see in the dark. Making that effort. When we turn off the light at night in our bedroom before going to sleep, it’s likely that our pupils don’t dilate, because we’re not trying to see the familiar objects around us, we just want to fall asleep. So even if we leave our eyes open for a brief period, they’re not actually trying to look at anything. It’s like when you enter a classroom and see a maths problem on the board. Your eyes won’t dilate just on noticing the problem, but only when you try to solve it.

Canto: I presume there’s been research on this – like with everything we ever think of. What I’ve found is that the ‘pupillary light reflex’ is described as part of the autonomous nervous system – an involuntary system, largely, which responds ‘autonomously’, unconsciously, to the amount of light it receives. But as you say, there are probably other over-riding features, coming from the brain rather than outside. However, a pupil ‘at rest’, in a darkened room, is usually much dilated. So dilation is by no means always to do with attention or focus.

Jacinta: Well there’s a distinction made in neurology between bottom-up and top-down processing, which you’ve just alluded to, in the sense that information coming from outside, and sensed on the skin, the eye and other sensory organs, is sent ‘up’ to the brain – the Higher Authority, – which then sends down responses, in this case to dilate or contract the pupil, all that is called bottom-up processing. But researchers have found that the pupil isn’t just regulated in a bottom-up way.

Canto: And that’s where cognitive pupillometry comes in.

Jacinta: And here are some interesting research findings regarding top-down influences on pupil size. When subjects were primed with pictures relating to the sun, even if they were’nt bright, their pupils contracted more than with pictures of the moon, even if those pictures were actually brighter than the sun pictures. And even words connected to brightness made their pupils contract. There’s also been solid research to back up the speculations of Eckhard Hess, that emotional scenes, images and memories, whether positive or negative, have a dilating effect on our pupils. For example, hearing the cute sound of a baby laughing, and the disturbing sound of a baby screaming, widens our pupils, while more neutral sounds of road traffic or workplace hubub have very little effect.

Canto: Because there’s nothing, or maybe too much info, to focus our attention, surely? While the foregrounded baby’s noises stimulate our sense of wonder, of ‘what’s happening?’ We’re moved to attend to it. Actually this reminds me of something apparently unrelated but maybe not. That’s the well-known problem that we’re moved to give to a charity when one suffering child is presented in an advertisement, and less and less as we’re faced with a greater and greater number of starving children. These numbers become like distant traffic, they disperse our attention and interest.

Jacinta: Yes well that’s a whole other story, but this brings us to the most interesting of findings re top-down effects on our pupils, and the question we’ve asked in the title. A more scientific name for thinking hard is increased cognitive load, and countless experiments have shown that increasing cognitive load, for example by solving tough maths problems, or committing stacks of info to memory, correlates with increased pupillary dilation. This hard thinking is done in the prefrontal cortex, but we won’t go into detail here about its more or less contested compartments. What I will say is there’s an obvious difference between thinking and memorising, and both of these activities increase cognitive load, and pupillary dilation. Some very interesting studies relating memorising and pupillary dilation have shown that children under a certain age, unsurprisingly, are less able to hold info in short-term memory than adults. The research task was to memorise a long sequence of numbers. Monitoring of pupil response showed that the children’s pupils would constrict from their dilated state after six numbers, unlike those of adults.

Canto: So, while we may not have a definitive answer to our title question – the why question – it seems to be that cognitive load, like any load that we carry, requires the expenditure of energy, which can be manifested in the tightening of muscles in the eye which dilates the pupils. This dilation reveals, apparently, that we’re attending to something or concentrating on something. I can see some real-world applications. Imagine, as a teacher, having a physics class, say. You could get your students to wear special glasses that monitor the dilation and constriction of their pupils – I’m sure such devices could be rigged up, and connected to a special console at the teacher’s desk, so he could see who in the class was paying close attention and who was off in dreamland…

Jacinta: Yeah right haha – even if that was physically possible, there are just a few privacy issues there, and how would you know if the pupillary dilation was due to the fascinating complexities of electromagnetism or the delightful profile of your student’s object of fantasy a couple of seats away? Or how could you know if their apparent concentration had anything much to do with comprehension? Or how would you know if their apparent lack of concentration was to do with disinterest or incomprehension or the fact they were way ahead of you in comprehension?

Canto: Details details. Small steps. One way of finding out all that is by asking them. At least such monitoring would give you some clues to go by. I look forward to this brave new transhumanising world….

References

Daniel Kahneman, Thinking fast and slow, 2012

https://kids.frontiersin.org/article/10.3389/frym.2019.00003

Torres A and Hout M (2019) Pupils: A Window Into the Mind. Front. Young Minds. 7:3. doi: 10.3389/frym.2019.00003

Written by stewart henderson

June 24, 2019 at 11:18 am

On Massimo Pigliucci on scientism 2: brains r us

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neuroethics is coming…

In his Point of Inquiry interview, Pigliucci mentions Sam Harris’s book The Moral Landscape a couple of times. Harris seeks to make the argument, in that book, that we can establish, sometime in the future, a science of morality. That is, we can be factual about the good life and its opposite, and we can be scientific about the pathways, though there might be many, that lead towards the good life and away from the bad life. I’m in broad agreement about this, though for pragmatic reasons I would probably prefer the term ‘objective’ to ‘scientific’. Just because it doesn’t frighten the horses so much. As mentioned in my previous post, I don’t want to get hung up on terminology. Science obviously requires objectivity, but it doesn’t seem clear to everyone that morality requires objectivity too. I think that it does (as did, I presume, the authors of the Universal Declaration of Human Rights), and I think Harris argues cogently that it does, based on our well-being as a social species. But Pigliucci says this about Harris’s project:

When Sam Harris wrote his famous book The Moral Landscape, the subtitle was ‘How science can solve moral questions’ – something like that. Well that’s a startling question if you think about it because – holy crap! So I would assume that a typical reader would buy that book and imagine that now he’s going to get answers to moral questions such as whether abortion is permissible and in what circumstances, or the death penalty or something… And get them from say physics or chemistry, maybe neuroscience, since Harris has a degree in neuroscience..

Pigliucci makes some strange assumptions about the ‘typical reader’ here. Maybe I’m a long way from being a ‘typical reader’ (don’t we all want to think that?) but, to me the subtitle (which is actually ‘How science can determine human values’) suggests, again, methodology. By what methods, or by what means, can human value – that’s to say what is most valuable to human well-being – be determined. I would certainly not have expected, reading the actual sub-title, and considering the main title of the book, answers to specific moral questions. And I certainly wouldn’t expect answers to those questions to come from physics or chemistry. Pigliucci just mentions those disciplines to make Harris’s views seem more outrageous. That’s not good faith arguing. Neuroscience, however, is closer to the mark. Our brains r us, and if we want to know why a particular mammal behaves ‘badly’, or with puzzling altruism, studying the animal’s brain might be one among many places to start. And yet Pigliucci makes this statement later on re ‘scientistic’ scientists

It seems to me that the fundamental springboard for all this is a combination of hubris, the conviction that what they do is the most important thing – in the case of Sam Harris for instance, it turns out at the end of the book [The Moral Landscape] it’s not just science that gives you the answers, it’s neuroscience that gives you the answers. Well, surprise surprise, he’s a neuroscientist.

This just seems silly to me. Morality is about our thoughts and actions, which start with brain processes. Our cultural practices affect our neural processes from our birth, and even before our conception, given the cultural attitudes and behaviours of our future parents. It’s very likely that Harris completed his PhD in cognitive neuroscience because of his interest in human behaviour and its ethical consequences (Harris is of course known for his critique of religion, but there seems no doubt that his greatest concerns about religious belief are at base concerns about ethics). Yet according to Pigliucci, had Harris been a physicist he would have written a book on morality in terms of electromagnetic waves or quantum electrodynamics. And of course Pigliucci doesn’t examine Harris’s reasoning as to why he thinks science, and most particularly neuroscience and related disciplines, can determine human values. He appears to simply dismiss the whole project as hubristic and wrong-headed.

I know that I’m being a little harsh in critiquing Pigliucci based on a 20-minute interview, but there doesn’t seem any attempt, at least here, to explain why certain topics are or should be off-limits to science, except to infer that it’s obvious. Does he feel, for example, that religious belief should be off-limits to scientific analysis? If so, what do reflective non-religious people do with their puzzlement and wonder about such beliefs? And if it’s worth trying to get to the bottom of what cultural and psychological conditions bring about the neurological networking that disposes people to believe in a loving or vengeful omnipotent creator-being, it’s also worth trying to get to the bottom of other mind-sets that dispose people to behave in ways productive or counter-productive to their well-being. And the reason we’re interested isn’t just curiosity, for the point isn’t just to understand our human world, but to improve it.

Finally Pigliucci seems to confuse a lack of interest, among such people in his orbit as Neil deGrasse Tyson and Lawrence Krauss, in philosophy, especially as it pertains to science, with scientism. They’re surely two different things. It isn’t ‘scientism’ for a scientist to eschew a particular branch of philosophy any more than it is for her to eschew a different field of science from her own, though it might seem sometimes a bit narrow-minded. Of course, as a non-scientist and self-professed dilettante I’m drawn to those with a wide range of scientific and other interests, but I certainly recognise the difficulty of getting your head around quantum mechanical, legal, neurological, biochemical and other terminology (I don’t like the word ‘jargon’), when your own ‘rabbit hole’ is so fascinating and enjoyably time-consuming.

There are, of course, examples of scientists claiming too much for the explanatory power of their own disciplines, and that’s always something to watch for, but overall I think the ‘scientism’ claim is more abused than otherwise – ‘weaponised’ is the trendy term for it. And I think Pigliucci needs to be a little more skeptical of his own views about the limits of science.

Written by stewart henderson

May 26, 2019 at 3:09 pm