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a bonobo world 30: touching on science, and adversarial systems

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I love this quote from Ernest Rutherford, the New Zealand ‘provincial’ who became one of the most brilliant experimental physicists of the turn-of-the century physics revolution:

… experiment, directed by the disciplined imagination either of an individual, or, still better, of a group of individuals of varied mental outlook, is able to achieve results which far transcend the imagination alone of the greatest philosopher.

from Thomas Crump, A brief history of science, p225

We’ve far transcended the bonobos in our experimental and tool-making skills, and in our varied mental outlooks, but it seems to me the teamwork is lacking, or at least it’s often outdone by over-competitiveness and mutual suspicion. Science, the bid to find the best explanations for our own workings and the working of the universe around us, and the best way forward for our species and all that connects with us, has long struck me as the best activity to unite us as Homo sapiens. Of course, the scientific community, being human, is driven by competition and personal glory to a large degree, but the smiles I see on the faces of Jennifer Doudna and Emmanuelle Charpentier, whose images are all over the internet at present, would hardly strike anyone as smug or self-congratulatory, and they’re clearly happy to share the glory and to educate anyone prepared to listen about the meaning of the CRISPR-Cas9 gene editing breakthrough, and to give all credit where credit is due to their collaborators and precursors. 

I’m not being naive here, methinks. Having read Venki Ramakrishnan’s Gene Machine and Meredith Wadman’s The Vaccine Race, and knowing of the battles over atomic theory which may have led to Ludwig Botzman’s suicide, I’m well aware that scientific competition can be pretty fierce. However, I don’t believe it’s anywhere near as ideological as politics or law. Generally the goal of science is something all scientists have in common – that best explanation. That is not the case with many other fields of activity. Here is what I wrote in 2011 about what I call ‘macho’ adversarial systems that continue to blight human society. 

1. Politics.

Some thirty years or so ago I read a book which had as profound a political influence on me as anything I’ve ever read. It was written by the Roman historian Livy and it bore the the title The history of the Roman Republic or something like that [in fact Livy’s monumental history, Ab Urbe Condita Libri, ‘Chapters from the Foundation of the City’ covered the whole ground from the myths of Rome’s founders to the early empire under Augustus, in Livy’s own time, and the book I read was presumably a translation of the first half or so]. What astonished me about the book, much of which was made up of speeches from political leaders [a trick he clearly learned from Thucydides] was, to me, its modern relevance. It told the story of two political factions or sides, or perhaps parties, the Patricians and the Plebeians, and of how political power swung from one side to another on a regular basis. However, as is the case in modern politics, this regularity wasn’t particularly regular. Depending on the persuasiveness and charisma of particular leaders, and on external pressures [and corruption of course also had a role], one side might hold sway for an extended period. Many of the issues discussed – taxation, wealth and land ownership and/or redistribution, security and military expenditure, had a familiar ring, and some approaches struck me as profoundly socialist, some two thousand years avant la lettre. Naturally all this made me consider the modern left and the modern right from a more interesting ‘longitudinal’ perspective. But another thing that struck me was the quite viciously adversarial world Livy described. When the political pendulum inevitably swung against them, those who were ousted from power were, equally inevitably, accused of treason, corruption, and/or both, and driven into exile or, probably more often, summarily executed or forced into suicide. Yet quite often their policies were followed by their successors, in spite of much rhetoric about ‘winding things back’. It all left me wondering why anybody in their right mind would pursue a public, political career under such circumstances. It may well have been that civic virtue, or the kudos gained from serving the public in the role of consul or quaestor, was regarded so highly that the inherent dangers were swept aside, or even seen as a worthy feature of the job [think of a career in the armed forces – heroism always has its appeal].

Domestic politics isn’t quite as threatening as it once was, but it still seems sometimes pointlessly adversarial. Notably, in many of the areas where a sensible person might expect a bipartisan approach, such as immigration and climate change, the parties are most determined to be at loggerheads. Maybe it’s because they’re so close together on these issues that they can see the whites of their enemies’ eyes, and this drives them into a frenzy of acrimony. It’s true that Tony Abbott appears to be a climate change ignoramus, but he’s also a pragmatist, and he knows that, if he finally gets in, he’ll have to come up with some sort of scheme to tackle climate change, and it won’t be heaps different from Labor’s. The rest is just spoiling, and an insult to the voters’ intelligence. As for the asylum seeker issue, it should be a minor one considering the numbers involved, but the opposition has whipped and frothed it up for all it’s worth, not caring about the fact that one day they’re complaining about the government’s softness, and the next day they’re decrying government inhumanity. As long as they get to hurl abuse. I know I’m not the only one who finds all this childish and patently dishonest, but most people seem to just consider it a political game that has to be played. I wonder why? Is it so that we can feel superior to all those dishonest pollies? Or is it that this really is the best way to forge policy and to make reforms, in the teeth of vehement opposition. Maybe being collaborative makes for worse policy, I don’t know. There just seems so much expense of spirit in a waste of shame.

2. Law

Again, I’m never sure if I’m missing something, but the adversarial legal system has always struck me as weird. I felt the same way about debating clubs as a kid – I had no interest in finding clever arguments for a position I didn’t believe in, I wanted to argue for what I believed, and to listen to others and gladly concede to them if their argument went deeper and uncovered things I hadn’t thought of. Getting to the truth, or to the most convincing and evidence-backed account, that was the thing. But of course there are other serious considerations with this approach to law. Some lawyers are more skillful, experienced and convincing than others, and lawyers can be bought. From a personal perspective, I can’t understand how a lawyer can do all in his power to defend or prosecute someone whose guilt or innocence he isn’t sure of, out of a ‘professionalism’ from which all moral qualms are removed, if that’s possible. This is probably naive of me, and I know that in these matters almost everyone is compromised by vested interest – the police want to see their arrests vindicated, the victims and their families want revenge, the lawyers want to improve their win/loss ratios, the accused want to get off, etc. Only the judge [and/or jury] is expected to uphold some sort of claim to objectivity, thus becoming the target of all the persuasive powers of the defence and prosecution teams, who seek to take advantage of every quirk and tendency they might perceive in the judge or the jurors. All of which makes me feel not quite right.

I know that in some countries a non-adversarial judicial system has been adopted, but I’m completely vague on the details. I do know that it’s a system heavily criticised by the proponents of the adversarial system, on what grounds and with what legitimacy I’m not sure. I’ve also heard that it hasn’t necessarily produced better or fairer outcomes. I’m also at a loss as to how such a non-adversarial system is financed, without accused persons being able to pay top dollar for the best lawyers. However, I can’t help but intuitively feel that a non-adversarial, collaborative system, in which everybody has the same aim, to uncover the truth surrounding a particular crime or alleged crime, would in principle be a better approach.

3. Work

I presume that ever since we began to divide labour – that is, from the beginning of civilisation – work and power have been intimately related. In fact, it’s only in recent times, with the growth of the idea of universal human rights and the notion of inherent, individual human dignity, that we’ve come to see that people shouldn’t necessarily be devalued according to the type of work they do. The otherwise brilliant Aristotle notoriously wondered whether slaves were capable of consciousness, and this, I would guess, was not due to their inherent status [he knew well enough, surely, that today’s battalion commander could become tomorrow’s slave to forces victorious over him], but to the menial work he or she was forced to do. Similarly when the novelist V S Naipaul [whose work and character I’ve always loathed] recently declared himself to be a superior writer to every female who has ever taken up a pen, he based this ‘knowledge’ on female work, as he saw it. Women, or women writers, had never been estate managers or big bosses or whatever, and so could never see things from a superior male perspective.This idea that employers were inherently superior to ‘underlings’ has only gradually faded with the advent of the union movement and its ability to articulate the rights and grievances of such underlings. Mostly this has involved clashes, demonstrations and strikes, with the formation of employer groups to combat the rise of workers’ associations.

I think it’s fair to say, though, that in the world of work we’ve seen more positive moves towards a collaborative approach than in other areas. Work, in the west, has become more multifaceted and less rigidly specified, with a blurring of distinctions between types of work and the prestige attached to work, from parental roles and household tasks to management and other high-flying positions, and this has broken down the old us-and-them tradition to some extent. Not that there isn’t a place for good old-fashioned confrontation. Sometimes, as with the demonstration I participated in recently, the problem is that there is no clear ‘enemy’. Workers in the community welfare sector [where the percentage of women is high] are very poorly paid. Generally they’re paid by the government, which means their work is very insecure as governments and their pet projects come and go. Funding is ever a problem and it’s hardly surprising that turnover is very high. Targeting government becomes a problem when governments get turfed out and the next government hasn’t made the same commitment. The problem may well be in public relations – but I’m moving too far from my focus. The point is that, again in this area, a collaborative approach, recognising the mutual dependency of coalface workers and management [and often their inter-changeability] strikes me as inherently more productive. But maybe we’ve had to go through a certain period of mutual hostility, misunderstanding and misrepresentation to get to that stage.

 

So the above is ten years old, and the world of work – the growing gig economy, and increasing deregulation – is getting tougher for those without the right connections. A basic income provision, which might alleviate the problems caused by an increasing concentration of wealth, doesn’t seem to be supported fully by the left or the right, never mind the kind of bipartisan support required for success. But bipartisanship and collaboration is essential to face and overcome the problems we’re creating for ourselves. The thirty percent target for female involvement at all levels in these key fields is critical in creating this collaborative environment – though thirty percent isn’t enough. 

 

Written by stewart henderson

March 3, 2021 at 12:43 pm

a bonobo world etc 28: finding connections through difference

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some of the language and cultural groups in modern China

Our human world is divided into many nations – 195 or so according to the UN, but this all depends on how you define the term. We know that there are many peoples who see themselves as separate and distinct from the nations they happen to inhabit, and prefer to consider themselves a nation of some sort, and some have named their nation – the Uyghurs of East Turkistan, the Kurds of Kurdistan, the Catalans of Catalonia, the Basques of Cantabria (and many other names) and the Samaritans of Samaria, to name a few – while others, such as the Hazaras, the Rohingyas, the Yorubas and the Tamils, may or may not have specific named territories they would like to claim as their own. In Australia, some have spoken of hundreds of Aboriginal nations, generally associated with language groups. And since we know of about 7,000 existent languages, each associated with particular cultures, there seems to be something of a barrier to any simplistic notions of globalism and global problem-solving. 

This is the difference between human apes and other apes. We have divided into distinct groupings, which it seems, our ancestral hominins, going back to CHLCA – the chimpanzee (and bonobo)-human last common ancestor – didn’t do. But is this true? Could it be that the neanderthals and others formed separate cultural groupings within themselves? And how is it that language, which creates such barriers among peoples today, became so diversified as we went forth and multiplied? 

Clearly language is a near-unique human capacity. The neanderthals, though, are now known to have possessed a hyoid bone – a horseshoe-like bone in the neck – which may argue for speech capacity. Hyoid fossils have also been found attributed to Homo heidelbergensis and dated back half a million years. If these extinct hominins had language, was it the same language? Language is a means not only of communication but of instilling and handing down cultural praxis, so who knows? The idea of sub-dividing Homo heidelbergensis, Homo neanderthalensis and perhaps others into distinct language and cultural groups really makes the brain spin. 

Today, with the greater ease of travel, and with the general tendency of humans, and most other species, to migrate from regions of great danger and few resources to regions of greater resources and fewer dangers, we find that the most economically successful countries are becoming increasingly multicultural, and naturally those countries seek to make a virtue out of necessity. 

There are clearly positives and negatives about multiculturalism. Minority cultures understandably seek the comfort of their familiars, leading to ghettoism. They also have vulnerabilities that are exploited by the dominant culture, taking on low-paid or under-the-counter work eschewed by others, and accepting poorer housing and other conditions. Discomfort with difference works both ways of course, and it has been the case that, going back to the days of the early slave-dependent cultures of Greece and Rome, slaves were considered something less than human even by the intelligentsia (and women in somewhat similar ways). The difference today is, or should be, that we know how nonsensical those attitudes were. And yet they persist, in muted form. 

There’s also the view, put forward for example by Sam Harris in The moral landscape and, in different form, by David Deutsch in The beginning of infinity, that some cultures are objectively superior than others, especially in terms of law, science and progress. Their general argument is that those cultures that are static or archaic in terms of lore and ideology need to ‘get with the program’ being followed by most developed countries in terms of the pursuit of deeper and richer knowledge and the tools and technologies that flow from that knowledge. And yet, paradoxically, some of that knowledge and research informs us that indigenous cultures in particular, such as existed for tens of thousands of years in Australia, developed practices and technologies over that period which allowed them to live in relative comfort in a landscape that new arrivals from Europe found inherently inhospitable – though of course those new arrivals didn’t by any means give up, and eventually found ways to exploit enough of the land and resources to become populous and dominant. 

In reflecting on all these differences and tensions, we need, I think, to always keep in mind how situated we are. None of us chose the cultures we were born into, and this heavy fact should help determine our sympathy for those born into more or less different cultures, as well as those born better or worse off in our own. And there are many features common in our humanity. As a teacher of international English, I’ve taught students from scores of different nations and cultures, and clearly from a range of different positions within those cultures, and I’ve been struck by the broad lines of humanity they share, in terms of humour, ambition, anxiety, desire and wonder. All of these emotions or traits are a kind of human substrate, a permanent foundation upon which human cultures, which come and go and transform and so forth, are constructed, sometimes obscuring the view of the basic humanity that really connects us. 

The language barriers may be about to erode, by means of technology – at least the barriers between major languages, such as Mandarin and English (the minority languages will inevitably get the rough end of this particular stick). Electronic translators are a long way from the Babel fish thought up by Douglas Adams in The hitch-hikers guide to the galaxy, a device like Apple’s AirPods which instantly translates every language in the universe into your own, but earpiece translators are already with us, and are bound to improve. It’s surely better than having everyone learn the same, dominant language. But the real promise of this technology is the promise of collaboration, and the reduction of truly artificial, or human-created, differences, and strengthening that human foundation that underlies those differences. Something to hope for. 

 

References

Madelaine Bohme, Rudiger Braun & Florian Breier, Ancient bones, 2020

https://www.bbc.com/news/science-environment-25465102

https://www.theguardian.com/technology/2019/feb/17/is-the-era-of-artificial-speech-translation-upon-us

Written by stewart henderson

February 9, 2021 at 2:13 pm

Covid-19: remdesivir, masks, vaccine trials, arrhythmias

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So to Dr Seheult’s coronavirus update 77, where he looks again at the antiviral drug remdesivir. A preliminary report from the New England Journal of Medicine describes results from trials comparing remdesivir with placebo in covid-19 patients at various levels of treatment, i.e, those receiving oxygen, those not receiving oxygen, those receiving high-flow oxygen or ‘noninvasive mechanical ventilation’, and those receiving full mechanical ventilation or ECMO (extracorporeal membrane oxygenation), and the finding was that remdesivir only made a statistically significant difference in the oxygen-receiving patients, which is more or less an intermediate phase. This may be due to the larger sample size that fell into this category. There were apparently small benefits in the non-oxygen category, but nothing in the more serious patient categories. The report’s conclusion:

These preliminary findings support the use of remdesivir for patients who are hospitalised with Covid-19 and require supplemental oxygen therapy. However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient.

So remdesivir appears to be just one of many agents and therapeutics in the armamentarium of health authorities dealing with this pandemic, which over the past few months appear to have been utilised to reduce mortality and improve recovery times since the early phase of the outbreak in the USA, to judge from figures comparing, say, New York with Texas and Florida.

The update also discusses heat-treating the interior of police vehicles as a disinfectant, using a computer program. Basically a system has been devised to heat-treat unoccupied vehicles for 15 minutes to 133 degrees fahrenheit, long enough and hot enough to kill 99% of known pathogens, including SARS-CoV2, and it’s already being rolled out for police SUVs. Interesting, and obviously adaptive to other circumstances. The rest of the update discusses promising approaches as of the end of May, including convalescent plasma therapy, which I hope to look at later.

Update 78 starts with face masks. We here in South Australia have only suffered 459 cases in total, with 457 recovered and only 4 deaths. The majority of cases by far occurred in the early stages (March-April), and much has opened up since then, and the wearing of masks has always been optional here. However, the virus has had a resurgence in Australia’s more populated eastern states, so we’re on alert, and there’s been a partial closing down again. Still, most people I notice aren’t wearing masks. In the USA there seems to have been some prevarication from authorities like the CDC on mask-wearing, but with a further understanding, especially of asymptomatic and pre-symptomatic cases, they came out more strongly in favour of cloth masks ‘in public settings where other physical distancing measures are difficult to maintain (e.g. grocery stores and pharmacies), especially in areas of significant community-based transmission’. The WHO’s guidelines aren’t so strict possibly because they’re dealing with a broader base in which effective face masks are less readily available and need to be prioritised.

Also related to masking is a New England Journal of Medicine article on aerosols and droplets generated by speech, which have been implicated in Covid-19 transmission. A simple experiment was conducted using laser light scattering to illuminate droplets from a speaker without a mask, and then with one, and the difference was quite dramatic. Update 78 shows the video, and it’s worth a thousand words.

This update also highlights a website which I intend to explore further, especially as I seem to be spending a lot of time in the world of disease, pathogens and the fight against them. It’s called Regulatory Focus, and there’s a further link to its covid-19 therapeutics tracker, which tracks all the research and studies, of antivirals, monoclonal antibodies and any other medications that might relate in any way to the pandemic, and another link takes us to the covid-19 vaccine tracker. It provides information on phase trials, the vaccine type, the institutions and sponsors involved, etc.

In update 79, Dr Seheult picks out a few of the vaccine trials that seem to show most promise and are most likely to be available by 2021. First is the Moderna mRNA-1273 candidate, which will inject mRNA to produce proteins that generate an immune response. Now the standard clinical trial process for testing a vaccine involves three phases. Phase 1 tests primarily for safety, phase 2 largely looks at appropriate dosage, and phase 3 is the final, large human population trial. These phases have been fast-tracked more than ever before, as is well known, sometimes without the usual animal testing, which would generally raise ethical issues, but that doesn’t seem to be happening for covid-19 trials. The University of Oxford candidate is ‘a chimpanzee adenovirus vaccine vector called AZD1222’. It injects an epitope for an antigen into the patient. An epitope is a region of an antigen that antibodies detect and bind to. Other candidates come from the Merck company, Johnson & Johnson and Pfizer.

Update 80 deals with a very controversial issue, which is possible research industry malpractice, in the form of massaged results relating to a relatively small company, Surgisphere. Interestingly, it involves an overstatement of deaths here in Australia, among other inconsistencies, which have led to retractions of papers on hydroxychloroquine and chloroquine in prestigious journals such as the Lancet and NEJM. It seems that the papers may have exaggerated negative effects from the use of these anti-malaria medications, with or without the addition of a macrolide (a class of antibiotics), which has just added to the controversy surrounding them. There’s also a question about the use of the anti-parasite drug ivermectin, and some common heart medications, due to these now-retracted results.

Interestingly, update 81, posted back on June 9, highlights Australia as still succeeding in keeping numbers down as we head into winter. That’s not the case today (August 11). It goes on to introduce another website, Covid-trials.org, comprising data on ‘over 1400 trials’ (now over 1900) worldwide relating to covid-19, including ‘alternative therapy’ and ‘traditional Chinese medicine’. Hmmm. And of course all the more promising treatments. This and the previously mentioned vaccine and therapeutics trackers provide a wealth of ongoing detail about the who, the how, the what, the how much, etc.

The update also describes a trial of hydroxychloroquine ‘as post-exposure prophylaxis’ published in NEJM. 821 people known to be exposed to the virus were treated with either hydroxychloroquine or a placebo, and then tested for the virus. The result was a non-statistically significant prophylactic effect. There were minor gastrointestinal side-effects in the hydroxychloroquine group, but no cardiac arrhythmias, often associated with the drug. Dr Seheult explains something about these arrhythmias, which is interesting enough for me to dwell on.

When we look at an electrocardiogram (ECG) we find something like the drawing here, with a P-wave, and a T-wave at the end. Some medications can cause a prolonged QTc (the c stands for ‘corrected’), and in combination with others, this can result in cardiac arrhythmias, which generally have two types, as shown in the illustration at the top of this post – an over-fast beat (tachycardia) or a too-slow one (bradycardia).

So, although the positive effects of hydroxychloroquine in this study were minor, there may have been a greater benefit from adding zinc to the treatment, as Seheult suggests, because the drug acts as a zinc ionophore. An ionophore is a fat-soluble transporter material which can carry non-fat-soluble minerals like zinc through the fatty cellular membrane. Zinc inhibits the RNA-dependent RNA polymerase of the coronavirus, but it seems that as of mid-June no full-blown studies had been done to show a benefit, or otherwise, from the combination.

References

Coronavirus Pandemic Update 77: Remdesivir Update; COVID-19 in Mexico

Coronavirus Pandemic Update 78: Mask Controversy; Vaccine Update for COVID-19

Coronavirus Pandemic Update 79: COVID-19 Vaccines to Keep an Eye On – mRNA, Antigen, Others

Coronavirus Pandemic Update 80: COVID-19 Retractions & Data (Hydroxychloroquine, ACE Inhibitors)

Coronavirus Pandemic Update 81: New Data on Hydroxychloroquine Side Effects & Prevention of COVID-19

https://www.nejm.org/doi/full/10.1056/NEJMoa2007764

https://jamanetwork.com/journals/jama/article-abstract/2766943

https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker

https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-therapeutics-tracker

https://covid-trials.org/

https://www.prnewswire.com/news-releases/studies-show-zinc-inhibits-viral-replication-but-theres-a-catch-301079772.html

Written by stewart henderson

August 12, 2020 at 1:10 pm

update 69: NAC, glutathione, oxidative stress, thrombosis

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glutathione – far more than just an antioxidant

So we start with a closer look at glutathione, and its backbone amino acid chain, including the amino acid cysteine. Cysteine has the formula HO2CCH(NH2)CH2SH. The thiol sub-chain (SH) is important because it can bind to another form of the molecule, with S binding to S (oxidised form) rather than binding to H (reduced form) as here. So, as Dr Seheult explains, if you have two glutathiones, in this reduced form (2GSH), oxidised via hydrogen peroxide (H2O2), you will create a bond (GS-SG) between the two oxidised glutathiones, together with water. This happens in the oxidisation processes in our cells.

Seheult next mentions ADAMTS13, which is also known as von Willibrand factor-cleaving protease, so it’s a zinc-containing enzyme. VWF polymerises via disulphide bonds, and ADAMTS13 can help in disrupting that process, I think. Seheult diverts us by mentioning the disulphide bonds that connect the spiral strands of keratin in hair. A ‘perm’ reduces the molecular structure, breaking the disulphide bonds, so that the individual strands can be straightened, or made more curly, after which ‘you neutralise the perm agent’?? via H2O2, allowing disulphide bonds to re-form keeping the new hair structure in place. That was almost interesting.

So what can we do to assist these glutathione-based processes in relieving oxidative stress? This is apparently where N-Acetylcysteine (NAC) comes in. This molecule, which is ‘the N-acetyl derivative of the natural amino acid L-cysteine’, is ‘an antioxidant and disulphide breaking agent’, according to a 2018 review article in the Journal of Free Radical Research (not a political journal). So NAC is a reducing agent, which, like cysteine, has an SH bond. It breaks disulphide bonds and adds hydrogen, reducing viscosity. NAC has been used as a mucolytic inhalant, and as an agent against tylenol (paracetamol) overdose. How this last effect works is complex and I’ll try to comprehend it.

As Seheult explains it, NAC would act on the metabolite of paracetamol in situations of overdose. In such cases the liver metabolises paracetamol via an alternative pathway, by means of the toxic metabolite NAPQI, which depletes the liver’s glutathione. NAC replenishes the glutathione, but I won’t try to analyse the mechanism here. The main point is that NAC’s glutathione-boosting effects may have potential in dealing with Covid-19 symptoms. According to the above-mentioned review article, glutathione depletion is related to oxidative stress associated with a wide range of illnesses and pathologies, as well as in general ageing. So, a 1997 study in Italy looked at H1N1 flu and NAC treatment in a randomised, double-blind trial of 262 individuals of both sexes, most of them suffering from non-respiratory chronic degenerative diseases. They were divided into a placebo group and a NAC tablet group for a period of six months. No difference was found in both groups contracting the virus, but the majority of the placebo group (79%) came down with symptomatic forms, compared to only 25% of the treatment group, a significant difference. The study concluded that NAC treatment ‘appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals.’

So, recognising that this update is 2-3 months old now, I went online to see if NAC treatment is being used, or more comprehensive trials are being undertaken, as I note that, though case-rates are still disturbingly high, especially in the USA, death-rates are somewhat reduced.

An article from NCBI (the National Center for Biotechnology Information), which post-dates update 69 by a couple of weeks, presents only a hypothesis:

that NAC could act as a potential therapeutic agent in the treatment of COVID-19 through a variety of potential mechanisms, including increasing glutathione, improving T cell response, and modulating inflammation.

However, it didn’t seem as if any effective clinical trials focusing specifically on Covid-19 had been completed at the time of the article. A much more recent article (July 14) in Future Medicine (not such a promising name, given the urgency), presents more biochemical detail of NAC’s action, along with the anticoagulant heparin, and mentions ongoing clinical trials, but not specific results. It also mentions NAC treatment as a preventive for frontline ICU workers and general healthcare workers. It may be that such treatment is already being applied.

So, returning to update 69, Seheult cites another article from 2010 in Biochemical Pharmacology which showed that NAC inhibited viral replication (here the virus was H5N1) and reduced inflammatory cytokines, and again they suggested it as a potential treatment in the case of future influenza pandemics. Another small trial suggested some limited efficacy for NAC in the treatment of acute respiratory distress syndrome (ARDS).

So on it goes. A 2018 article found that ‘[NAC] improves oxidative stress and inflammatory response in patients with community acquired pneumonia [CAP]’. This oxidative stress reduction may be more important for Covid-19 cases because of the possibility of thrombosis due to the effect on VWF. A 2013 study found a significant decrease in a number of coagulation factors with NAC treatment. Of course, with this blood-thinning facility, NAC should not be used for patients with increased bleeding risk during or resulting from surgery. In any case I note that NAC is on the WHO list of most safe drugs or treatments.

And there are more studies. Another 2018 study found that NAC could reverse cerebral injury from strokes exacerbated by diabetes. The study concludes that ‘the diabetic blood and brain become more susceptible to platelet activation and thrombosis’, and that NAC appears to offer protection against the risk of stroke. The study’s explanation of the process here gives me an opportunity for further revision:

[NAC protects against stroke] by altering both systemic and vascular prothrombotic responses via enhancing platelet GSH, and GSH-dependent MG elimination, as well as correcting levels of antioxidants such as SOD1 and GPx-1.

So that’s platelet glutathione, and glutathione-dependent methylglyoxal, and the antioxidants mentioned are superoxide dismutase 1 and glutathione peroxidase 1. The ScienceDirect website does an amazing job of informing us about every known aspect of molecular biochemistry, just saying. Its material on glutathione and its catalysis is exhaustive and exhausting. And it looks as though the silver lining to the tragedy of Covid-19 may be a spike in further research into this and other essential elements of the molecular basis of immune systems.

Dr Seheult goes on to cite one more study, which found that ‘NAC administration promotes lysis of arterial thrombi that are resistant to conventional approaches…’, principally by acting on VWF, and that it is even more effective in combination with ‘a nonpeptidic GpIIa/IIIb (glycoprotein) inhibitor’, with no observed worsening of symptoms or outcome vis-a-vis normal haemostasis.

So I’ll end this piece wondering how things are going with NAC and other applications to reduce both respiratory and thrombotic symptoms in regions where the virus continues to be spread through a mixture of government, business and personal irresponsibility and stupidity. The battle to keep people alive and relatively healthy will, I think, ultimately win over the stupidity of some, but at a terrible and tragic cost. Vaccines are in the offing, but fear, indifference and ignorance will probably have the most adverse influence on their effectiveness.

References

Coronavirus Pandemic Update 69: “NAC” Supplementation and COVID-19 (N-Acetylcysteine)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261085/

https://www.futuremedicine.com/doi/10.2217/fmb-2020-0074

https://www.sciencedirect.com/science/article/pii/S0304416512002735

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/methylglyoxal

Written by stewart henderson

August 2, 2020 at 12:46 pm

The bonobo world: an outlier, but also a possibility 2

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Definitely one of the best introductions to the bonobo world is Frans De Waal’s 2006 essay for Scientific American, available online. It describes a species that branched off from its chimp cousin some two million years ago. Although genetic researchers have made it known that humans are equally related to chimps and bonobos, we’re beginning to realise that a basic bean-count of genes shared may be an overly simplistic approach to measuring our connectedness with other species. In any case we still have much to learn from both of our closest living relatives, especially in terms of our social relationships. We have of course developed a culture, or a range of cultures that are much more diverse and dynamic than our primate cousins, which is some cause for optimism. We are, I hope, always learning better how and what to learn.

I believe it is very much worth looking at chimps and bonobos, not as opposites, which of course they aren’t, nor quite as models for humans to compare themselves to, but as two of many possible forms of our species in an earlier stage of cultural development. The fact is, and I should think this is unarguable, early humans, in their territoriality, their aggression, their gender-based division of labour, and their ownership fetishism, have largely developed from the basic cultural outlook of chimps rather than bonobos. Our history is marred by mostly male violence and hubris, and the power of possession, formerly of land, latterly of resources and technological know-how, and their transformation into financial power and influence, leading to systemic inequalities and a cult of selfishness.

But of course human culture isn’t one thing, and it has been subject to dizzying developments in modern times. Most astonishing is the growth of knowledge and its availability and rapid dissemination in the internet age. I’ll be taking advantage of that growth and availability in what follows.

One of the most interesting questions about bonobos and their largely female-dominated society is how that society came about, considering that bonobo females, like chimps, gorillas and humans, are smaller than the males. Clearly, size and attendant strength is an advantage in the kinds of environments early humans and their primate cousins had to deal with. We have no clear answer to this question, though it’s noteworthy that the bonobo diet, being less meat-heavy than that of chimps, would require less aggressive hunting, and strength to overcome prey. This raises the question – did the rise of females lead to a less carnivorous diet or was it the other way around?

First, let’s look at the bonobo diet. They are very much tree-dwellers, and fruit always forms a large part of their diet, but also leaves, seeds and flowers. Animal foods include worms and some insects, and the occasional snake or flying squirrel. This suggests that they rarely go on hunting expeditions. The bonobo habitat is generally more forested than that of chimps, and they spend more time in the tree-tops, harvesting the food they find there. It could be that the physical habitat of chimps, which is relatively more savannah-like, actually led to a more spread-out, competitive culture, compared to the closer-knit bonobos in their denser, tighter environment. If this is true, it’s reasonable to infer that the strength advantage of the lager males might be diminished by habitat. Perhaps, given a few million more years, the size difference between males and females may reduce. I may look at sexual dimorphism more generally in a later post.

Using bonobos as a guide to potential human behaviour often meets with strong push-back. I’ve experienced this myself in a number of conversations, and usually the argument is that we are so far removed from our primate cousins, and so much more culturally evolved, and diverse, that comparisons are odious. However, I suspect much of this is due to an arrogance about our sophistication which prevents us from learning lessons, not only from other primates but from other cultures that we deem inferior, even without consciously acknowledging the fact. Yet we are learning those lessons, and benefitting from them. Generally speaking, we – I mean those from a WASP perspective, like myself – are recognising that indigenous or first nation cultures were far better adapted to their environments than the later white arrivals – and that this adaptation was hard-won over many generations, during which a collective bank of experience developed. In ‘The Teachable Ape’, a chapter of his book She has her mother’s laugh, Carl Zimmer tells the tale of the ‘ill-fated’ Burke and Wills expedition which attempted to cross Australia from south to north in the 1860s. The team was heavily but inappropriately provisioned, even carrying Victorian-era furniture to make their campsites comfortable, but more importantly they weren’t anywhere near culturally prepared for spending long months in the arid landscape of central Australia. A starving remnant of the group stumbled onto a settlement of the Yandruwandha people, who had been living more or less comfortably from the land, in what is now the northern region of South Australia, just south of Cooper Creek, for tens of thousands of years. The Yandruwandha helped the Europeans out, allowing them access to their watering holes and feeding them fish, nardoo bread or porridge, and whatever they might bring back from their hunting trips. But sadly, tensions rose due to the arrogance of at least one of the Europeans, apparently humiliated at being forced to rely on ‘savages’ for survival. The Yandruwandha walked off, leaving the newcomers to their fate. Zimmer ends his tale with these words:

Burke and Wills were celebrated with statues, coins and stamps. Yet their achievement was to have died in a place where others had thrived for thousands of years. The Yandruwandha got no honours for that.

C Zimmer, She has her mother’s laugh, p451

Zimmer, of course, is correct, but it’s doubtful that his words would’ve been written, thought or accepted in the early 20th century, say halfway between the Burke and Wills tragedy and today. We’ve made vital progress, especially in the past 50 years, in recognising the adaptive intelligence of human cultures very different from our own, and even of other species. We can learn from them as we too have to adapt to different human environments, such as the post-industrial, technology-heavy, rapidly-renovating society we associate with ‘the west’. The roles of men, women, children, families and other human types and configurations are up for re-evaluation as never before.

References

https://ielc.libguides.com/sdzg/factsheets/bonobo/diet#:~:text=Honey%2C%20eggs%2C%20soil%2C%20mushrooms,small%20mammals%20(young%20duiker).

https://www.scientificamerican.com/article/bonobo-sex-and-society-2006-06/

https://www.britannica.com/animal/bonobo

Carl Zimmer, She has her mother’s laugh: the powers, perversions and potential of heredity, 2018.

Written by stewart henderson

July 20, 2020 at 3:05 pm

Covid 19: hopes, failures, solutions

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under pressure

Covid-19 continues to be devastating, especially in the USA, where there are vastly more cases than anywhere else, and vastly more deaths, though the picture there is complex. The hardest-hit region, the New York area, is seeing devastation in poorer districts such as Queens, where the Elmhurst public hospital is inundated with uninsured, critically ill patients. New York has suffered almost half of US deaths. Some other states and regions, especially physical outliers such as Alaska, Hawaii and the Virgin Islands, have very low numbers, and it would be hard to explain why the spread of cases across the mainland has been so uneven. Of course it’s obvious that there has been no federal leadership on the pandemic.

Here in Australia, where the numbers seem to be improving (we’re 33rd on the list of total cases, down from 18th when I first started paying attention to the list about three weeks ago, and 52nd on the list of total deaths), our conservative federal government is keen to open up the country again, and has released modelling to the effect that the virus will be eliminated from the mainland if we maintain current physical distancing measures, though it’s likely to take weeks rather than months:

The model suggests that every 10 people infected currently spread the virus to five more people, on average. At that level, the virus would eventually be unable to circulate and would die out within Australia.

Sydney Morning Herald, ‘Australia in course to eliminate Covid-19, modelling shows’

Australia’s current reproduction number (R0) is just a little over .5. A maintained R0 of 1 or less will eventually eliminate the virus. Of course, there will be fluctuations in that number, so it will be difficult to project a time when things are ‘all clear’. Another difficulty with modelling is that the number of infected but asymptomatic people is unknown and difficult to estimate. For example, recent Covid-19 testing of the entire crew of the aircraft carrier Theodore Roosevelt found that a substantial majority of those who tested positive were asymptomatic, casting doubt on previous estimates (already worrying for transmission) of one in four cases being asymptomatic.

The asymptomatic/presymptomatic transmission issue was addressed by Bill Gates in this article back in February. It’s what makes SARS-CoV-2 a much more serious threat than the previous SARS and MERS viruses. Gates, in this very important article, also provides an outline of what needs to be done globally to fight this pandemic and to prepare for inevitable future ones. If only…

It’s worth comparing Gates’ call for national and global co-ordination, and more expenditure, in the fields of epidemiology and disease prevention, with another more recent article, also published in the New England Journal of Medicine, which tells a tale of Britain and its NHS, gutted by years, in fact decades of ‘reforms’ and budget cuts:

Thanks to government “reforms” of the NHS, it has become highly decentralized, with over 200 commissioning groups in England that can make independent decisions about staffing and procurement of equipment — far from the monolithic “socialist” health care system it is often assumed to be. The devolved governments in Wales, Scotland, and Northern Ireland have substantial health system autonomy. At a time when central management of staff and resources might be most helpful, the decentralized decision-making structure leads to competition for resources and inconsistent policies.

One can hope that the travesty of this virus, especially in places like the US and the UK, will lead to a rethinking of the importance of a well-funded, centralised, co-ordinating and interventionist government in modern states, with particular emphasis on the healthcare system. But I suspect that, in the USA at least, things will go the other way, and the government-hating and government-blaming will only intensify. I’d love to leave this topic and look at solutions – that’s to say I’d love to focus more on the science, but I’m barely equipped to do so. Still, I like to have a go. A very technical and comprehensive review review of pharmacological treatments has been posted recently on the JAMA website, which includes an account of how SARS-CoV-2 enters host cells and utilises those cells for reproduction.

The review claims that currently the most promising therapy is the antiviral drug remdesivir. So what is it and how does it work? I’ll try to answer that question next time.

References

https://www.news.com.au/world/coronavirus/global/epicentre-of-the-epicentre-this-queens-ny-hospital-is-coronavirus-ground-zero/news-story/6d0213ab9d5dd82fa12339f551be99ce

https://www.theguardian.com/world/ng-interactive/2020/apr/16/coronavirus-map-of-the-us-latest-cases-state-by-state

https://www.smh.com.au/national/australia-on-course-to-eliminate-covid-19-modelling-shows-20200416-p54kjh.html

https://www.nejm.org/doi/full/10.1056/NEJMp2005755?query=recirc_artType_railA_article

https://www.nejm.org/doi/full/10.1056/NEJMp2003762

https://jamanetwork.com/journals/jama/fullarticle/2764727

Written by stewart henderson

April 18, 2020 at 1:18 pm

gods, science and explanation

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If you think that it would be impossible to improve upon the Ten Commandments as a statement of morality, you really owe it to yourself to read some other scriptures. Once again, we need look no further than the Jains: Mahavira, the Jain patriarch, surpassed the morality of the Bible with a single sentence: ‘Do not injure, abuse, oppress, enslave, insult, torment, torture, or kill any creature or living being.’ Imagine how different our world might be if the Bible contained this as its central precept.

Sam Harris, Letter to a christian nation

Reading David Deutsch’s The beginning of infinity, together with a collection of Stephen Jay Gould’s essays, Dinosaur in a haystack, has reminded me of my critique of Gould’s bad NOMA argument, which I reread lately. So here’s a revisiting and a development of that critique.
Put very simply, Gould argued that religion was about moral and spiritual matters, and that science was about causes and effects in the natural world, and that these spheres of interest didn’t overlap, so co-existence was not only entirely possible but mutually beneficial.

In his argument, I noted, Gould generally avoided mentioning gods, or God. It seems to me now, that this is more of a problem than I thought at the time, because religions are all about gods. While I don’t want to be hard and fast about this, religions really don’t exist without gods. In that sense, you might call Buddhism a spiritual belief system or worldview or discipline, but it isn’t a religion. It doesn’t use gods to explain stuff. And Confucianism even less so. Certainly in earlier times, in a more god-besotted world, Buddhism and even Confucianism were associated with or could be easily assimilated with local deities in China, Korea and Japan, and the world of morality was generally associated with portents and god-induced ‘disasters’, but that was to be expected in a pre-scientific climate, which prevailed globally for most of human history.

This is the point. For century upon century, gods, their behaviour, powers and attitudes or natures, were the explanations for war, famine, disease and the everyday accidents that humans suffered from. Even as some medical and other knowledge developed, the will of the gods was always there as a background explanation for the otherwise inexplicable. And so it shouldn’t be surprising, in a world teeming with god-explanations, that the pioneers of more earthly, measurable and testable explanations for phenomena still clung to this background of god-explanations for so much of what they saw around them – the birds in the sky, the food that sprang from the ground or hung from the trees, the life-giving rain, the failed harvests, the floods, the plagues, the invasions and so on.

Nowadays, what we call science can provide better explanations in every area we can think of than do god-explanations, and this is a major blow to religion and its relevance in the modern world. I would describe it as a death-blow. Indeed gods aren’t just bad explanations, they’re not really explanations at all. Why gods, after all? What are they, and where do they come from? No coherent explanation can be offered for them. Of course the obvious answer is that they come from the human imagination, as is evidenced by the human qualities they display – the beauty of the love-goddess, the long-bearded father-god, the thunderous dyspepsia of the war-god and so forth – but such an explanation is anathema to religion, as it collapses the house of cards. So an attempt is made to divert attention from inquiring into the ineluctable mystery of the god’s existence – sometimes by making such inquiries a kind of sacrilegious abomination – and to focus more on the god’s commandments. This is a move made by many a staunch Catholic.

I’ve heard such people say that the ten commandments of the Old Testament are clearly the basis of all our laws and morality. I’d like to have a look at them, particularly in terms of explanation. As young children, we’re often given commands – do this, don’t do that – by our parents. These commands generally have an explanation supporting them, which we learn later. But the explanations are essential, and commands without effective explanations to support them are surely a form of tyranny – at least that’s how I see it.
So let’s have a look at these commandments, which are so essential to ‘western’ or ‘civilised’ morality, according to some. I’ve put them in my own words.

  • 1. I’m your god, you mustn’t have other gods before me.
    This has nothing whatever to do with morality as far as I can see. This god says elsewhere that he’s a jealous god, and this is further proof. Catholics gloss this commandment as a commandment against idolatry, but that’s highly problematic because it makes the enormous assumption that the god called God is not an idol. If he’s saying ‘I’m the true god, all the others are fake’, he needs to provide proof. He doesn’t – and presumably makes the arrogant claim that he doesn’t need to.
  • 2. You mustn’t take my name in vain.
    So what is this god’s name? God, apparently. It’s like a marketing ploy, as if MacDonalds got to change their name to Hamburger and could take action against anyone else who used the name. In reality the god now called God was an amalgam of Hittite and Armenian gods, forged into a monotheistic being by elites of the region somewhere around the 7th century BCE. The idea of the commandment is that you should speak his name respectfully. Why? Because he’s God. The only way to avoid a circular argument here is to provide proof of this god’s existence, which hasn’t been done and can’t be done. There’s no morality on display here.
  • 3. The sabbath day should be kept holy.
  • This is fairly arbitrary, the word coming from the Hebrew sabbat, meaning rest, and it’s based on God’s rest day, as he created the universe or multiverse or whatever in six days and rested on the Saturday, according to Judaic tradition, but Christians arbitrarily changed the day to Sunday. Of course no educated person today thinks the world, universe, or whatever, was created in a week, whatever you define a week as, by an ethereal being. Again, this could only have moral effect if you believe in this creation story and the god at the centre of it (and if you believe the god is egotistical enough to want to be eternally remembered and acknowledged in this way).
  • 4. Honour your parents.
  • As a heuristic, this makes sense, but it is not a given. Some parents kill their children, others do irreparable damage to them. The vast majority, of course, don’t. This is a matter of individual cases and analyses. The complexity of parent-child relations is dealt with most profoundly by Andrew Solomon in his great book Far from the tree. I would refer everyone to that book as a response to the fourth commandment.
  • 5. You mustn’t kill.
  • This again is too vague, as it doesn’t deal with self-defence and other exculpating circumstances. It’s also fairly commonplace, and common-sense. It’s easy to find supporting explanations. Nobody needed this commandment to create laws regarding murder and unlawful death.
  • 6. You mustn’t commit adultery.
  • A lot can be said here. At the time that these commandments first appeared, and for a long time afterwards, women and girls were treated as chattels and very often married off against their will, sometimes as children, to men twice or thrice their age. Considering such a context, and considering that contraception was essentially non-existent in those days, adultery was generally treated differently depending on wealth, social status and gender. There might have been an explanation for the law of adultery, but it probably had more to do with property and the status of offspring than morality per se.
  • 7. Don’t steal
  • The concept of private property would have emerged slowly, and would have been interdependent on other cultural developments in the move from horizontally to more vertically based cultural systems. Even so, it’s unlikely that a prohibition on stealing would’ve been novel when this commandment was formulated.
  • 8. Don’t lie
  • the telling of lies to advantage oneself and disadvantage others would have been a problem at least since effective languages developed, and we have little evidence as to how long ago that happened. We certainly know it was long before the 6th or 7th centuries BCE, so there’s nothing new here. Again, though, the commandment is too vague to be particularly effective.
  • 9. Don’t covet (lust after) your neighbour’s wife
  • These last two commandments are about thoughts, which makes them particularly ineffectual. They might be interpreted as advice, which would leave us with fewer commandments to criticise, but even as advice they seem like so much pissing into the wind. And of course the fact that wives and not husbands are singled out is an indication of the particularism of the patriarchal society this commandment addresses.
  • 10. Don’t covet (hanker after) your neighbour’s goods.
  • Again, hardly a profound or memorable commandment, and barely relevant to today’s society. If you’re impressed by your neighbour’s car, for example, you might ask her about it, check out its performance and decide to get something similar yourself. What’s the big deal?

I’ve spent too much time on this, but I simply wanted to point out that, while gods are what religion is all about, they are, or were, also used as explanations. That’s in fact what they were for. And a ‘commandment’ is simply an explanation once removed, because they represent the god’s will. The explanation, therefore, for bad tidings or bad karma or whatever, becomes failure to follow the will and the commandments of some particular god or other.

Nowadays we have better explanations, based on what we know of human psychology and neurophysiology, and of how we work together in societies, as the most socially constructed mammals on the planet. We also know much more about how the physical world works, which has resulted in technological developments of increasing reach and sophistication. The idea that knowing so much more about what we are has no relationship to what we should do – the moral sphere – has always struck me as preposterous. This old is-ought separation was key to Gould’s NOMA thesis. But it’s not only that science’s increasingly far-reaching accounts of ourselves and the universe we live in is essential to our decisions about what we should do. It’s also true that religion keeps trying to tell us what we are. And its account s just don’t stack up, from the broadest scientific perspective. It just fails comprehensively as an explanation.

Written by stewart henderson

March 20, 2020 at 2:58 pm

the autodidact story 1: family and authority

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When I was young I was somewhat troubled about myself. I was unhappy at home, I hated school, I felt I had no-one to talk to, and my only solace was the ‘rich inner life’ that, much later, I read about in an essay by the philosopher Hilary Putnam. That’s to say, he wrote an essay in which he happened to mention that some outwardly nondescript people might have cultivated a rich inner life, or words to that effect, and this fairly mundane observation was the only thing I took from Putnam’s essay.

I had a difficult time with friendship, and still do. On my birthday – I was probably fourteen – I received a card from another boy I knew well. It read ‘to my best friend ever’. I read it with shock. It made me feel somehow ashamed and miserable. I felt that this friend of mine was deluded, and I’d been the cause of his delusion. Perhaps there was some arrogance in this – I felt that my ‘rich inner life’ was almost completely hidden from him, and everyone else, so how could he think he knew me well enough to consider me his BFF? However, when he left for England with his family a few months later I felt more alone than ever. 

I’ve never felt seriously suicidal, but I do recall a particular moment, when I thought, ‘this is who I am – a loner. I have to learn to live with it’. I cried myself to sleep, and went on. 

Of course, all autobiographies, whether short or long, are mostly lies, beautiful or otherwise, so don’t take any of this too seriously. My parents didn’t get on too well, to put it mildly, and my siblings were – rivals. We lived in one of the most thoroughly working-class regions of Australia, in the newly created town of Elizabeth, built around the manufactory of holden cars, now deceased. My father worked there for a brief time, but he didn’t like working in factories, and I don’t blame him, having worked in quite a few myself. Unfortunately he couldn’t think of anything else to do, so he didn’t do anything much, and my mother was the nagging, harried breadwinner. My relationship with both of them during my teen years could fairly be described as toxic.

We did have books however. Encyclopedias, classics, and surprisingly modern fare, especially in the new feminist line, such as The female eunuch, Patriarchal attitudes, The feminine mystiquue and The second sex. I don’t know where all these books came from, they just always seemed to be there. My mother insisted on getting us to the library regularly, for which I’ll always be grateful, but I rarely saw her reading anything. She had a higher-up job in the nursing profession and when she got home she’d always flip the TV from the ABC to her favourite sit-coms, I love Lucy or The Dick Van Dike show. As for my father, I often wondered if he knew how to read. But these people bestowed upon me their genes, more or less equally, and that was a source of wonder. Was I smart?

We had come to Australia as ten pound migrants, and I had flickering memories of the boat trip – a camel train on the banks of the Suez, being saved from drowning in the ship’s pool, sitting with a group of kids while my mother, seconded as an educator, taught us spelling or something.  

Education. I became a teenager in 1969. It was a fantastic time for music, and the culture that came with it. I looked out the window at my brother and his friends and they were all wearing levis and it looked so cool. My older siblings were buying records – the Beatles, the Kinks, the Stones, and some now-embarrassing singles like ‘Little Arrows’ by Leapy Lee. Not long afterwards came Dylan and Cohen and I loved all that cool verbiage. Was I smart? I didn’t like school. I couldn’t talk to the teachers like other kids. I didn’t like the inequality, that they might know more than me. I didn’t like being told what to do. I liked to read, to learn stuff in my own way. I didn’t have an imaginary friend exactly, but I was always talking and arguing in my head, and felt the lack of the real thing.  

One day I was somehow invited to some kid’s house whose older sister was visiting from university. Did she live in the university? There was a crowd of kids and I could just see glimpses of the girl-woman through arms and legs. She was sitting on a stool as on a pedestal and she was slim and pretty with neat blonde hair and lipstick and a neat plaid skirt and heels, and I was shocked at this first ever sight of a university student. They were supposed to wear jeans and sandals and tie-dyed t-shirts and be beautifully scruffy and hairy. Disappointing.

Anyway, I left school because I was always in trouble for not doing my homework, inter alia, and I had horrible fights with my mother when she wasn’t having horrible fights with my father, and my father had fist fights with me, which wasn’t much fun as he’d been a boxer in his past and I could see him eyeing me for maximum damage with his dukes up. I would stay at friends’ houses here and there, and I got my first job on an assembly line making Wilkins Servis washing machines. The one shown is of course a much earlier model than the ones I tended to stuff up when I worked there.     

And so my first experience of formal education was botched, and maybe I should blame myself, I don’t know. I continued to read of course, and to argue with myself. A rich inner life.

I read novels, mostly, in those days. I developed an obsession with Thomas Hardy. This was in my fifteenth year, I think. The Return of the Native was my first, and I think I read every single novel except A Laodicean, which critics said was his worst. I wanted to read it, for completeness, like Two Gentlemen of Verona, which I did read. I also wanted to know why it was considered so bad. I loved Thomas Hardy, he was so kind, it seemed to me, and so sad somehow.

(to be continued)

Written by stewart henderson

February 28, 2020 at 7:30 pm

epigenetics and imprinting 5: mouse experiments and chromosome 11

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something new, since Carey’s book was published – a healthy mouse, from entirely maternal DNA, with healthy offspring – and in 2018 a healthy bi-paternal mouse was created

 

So we were looking at how we – mammals amongst others – are engaged in a kind of battle for the best way to ensure our genetic survival into the future, beyond our insignificant little selves. This battle begins in the very early phase of life, as zygotes multiply to form a blastocyst. 

Remember from my last post on this topic, the male mammal is interested in the offspring above all else. He’s even happy to sacrifice the mother for the sake of the child – after all there’s plenty more fish in the sea (or mammals in the – you know what I mean). The female, on the other hand, is more interested in self-preservation than in this pregnancy. She wants more than one chance to pass on her genes.

So, by the blastocyst stage, cells have differentiated into those that will form the placenta and those that will form the embryo itself. Experiments on mice have helped to elucidate this male-female genetic struggle. Mouse zygotes were created which contained only paternal DNA and only maternal DNA. These different zygotes were implanted into the uterus of mice. As expected, the zygotes didn’t develop into living mice – it takes DNA from both sexes for that. The zygotes did develop though, but with serious abnormalities, which differed depending on whether they were ‘male’ or ‘female’. In those in which the chromosomes came from the mother, the placental tissues were particularly underdeveloped. For those with the male chromosomes, the embryo was in a bad way, but the placental tissues not so much.

In short, these and other experiments suggested that the male chromosomes favoured placental development while the female chromosomes favoured the embryo. Thus, the male chromosomes are ‘aiming’ to build up the placenta to drain as many nutrients as possible from the mother and feed them into the foetus. The female chromosomes have the opposite aim, resulting in a ‘fine balance’ in the best scenarios.

Further work in this area has identified particular chromosomes responsible for these developments, and some of the epigenetic factors involved. For example, mouse chromosome 11 is important for offspring development. When the offspring inherits a copy of chromosome 11 from each parent, the offspring will be of normal size. If both copies come from the mother it will abnormally small, while if both come from the father it will be abnormally large. These experiments were carried out on inbred mice with identical DNA. Nessa Carey summarises:

If you sequenced both copies of chromosome 11 in any of the three types of offspring, they would be exactly the same. They would contain the same millions of A, C, G and T base-pairs, in the same order. But the two copies of chromosome 11 do clearly behave differently at a functional level, as shown by the different sizes of the different types of mice. Therefore there must be epigenetic differences between the maternal and paternal copies of chromosome 11.

So this means that chromosome 11 is an imprinted chromosome – or at least certain sections of it. This is the same for other chromosomes, some of which aren’t imprinted at all. But how is it done? That’s the complex biochemical stuff, which I’ll try to elucidate in the next post on this topic.

Footnote: the photo above shows a bi-maternal mouse with healthy offspring, and further work in deleting imprinted genetic regions has allowed researchers to create healthy bi-paternal mice too. There’s a fascinating account of it here.

References:

Nessa Carey, The epigenetics revolution, 2011

https://www.the-scientist.com/news-opinion/first-mouse-embryos-made-from-two-fathers-64921

Written by stewart henderson

January 19, 2020 at 12:26 pm

the boy in the white palace 2: thoughts on Judge Howell’s decision in the Columbia District Court

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Beryl A Howell, Chief Judge, District Court of Columbia

Canto: So I’ve read the decision by the Chief Judge of the District Court of Columbia, which waved away the claims of White Palace lawyers, representing their Department of Justice (DOJ), ‘that existing law bars disclosure to the Congress of grand jury information’. Now, neither of us are lawyers, and I’d never heard of a grand jury before being drawn like a ghoul to the disaster of the bullish boy in the White Palace china shop – so reading this decision has been another of those steep learning thingies.

Jacinta: Yes, the grand jury concept does sound very grand, and a bit Olde Worlde, and I’ve discovered that it’s essentially an obsolete British thing, going back to Magna Carta at least, but now fallen into disuse except in two countries, the Grande Olde US of A, and, would you believe, Liberia. They appear to be a blunt tool of government, and another ‘only in America’ thing, almost. Here’s what an Australian academic blog, the conversation, has to say about it:

The main concerns about the process are that it is run by the prosecutor, no judge is involved, jurors are not screened for bias or suitability, the defendant is not present or represented, the prosecutors and grand jurors are prohibited from revealing what occurred, and transcripts of the proceedings are not made available.

So why does it exist at all? Well, it’s made up of ordinary citizens, rather than uppity legal folks – a grand jury consists of 16 to 23 people, unlike the petit jury made up of the standard dozen – so I suppose they thought it more democratic. They have to decide whether there’s enough evidence to charge someone. It’s like a pre-jury jury. But you can surely see from the above quote that it can be easily manipulated. And has been.

Canto: So this Judge Howell had to decide – but her decision isn’t final because it can be appealed, I believe – whether the DOJ was right in claiming that grand jury info (much of it redacted in the Mueller Report) should be handed over to the House Judiciary Committee (HJC).

Jacinta: So it’s a battle between the HJC and the DOJ, and may the best TLA win…

Canto: Judge Howell is in no doubt about the matter. ‘DOJ is wrong’, she writes multiple times in her 75-page judgment, in which she goes back to the findings of the Mueller Report. It’s funny, we’ve read that report but it’s so refreshing to be reminded of all the damning evidence, and the redacted stuff in part 1 which raised so many questions. There’s been so much that’s happened since, or so much that hasn’t happened that should’ve happened, that we’re inclined almost to believe that Mueller’s findings were unable to lay a glove on the White Palace incumbent, when the truth is far more sinister – that the whole US nation seems to have connived in allowing the boy-king to get away with everything, simply because he’s the King.

Jacinta: Well, I’m not sure about the whole nation, but of course you’re right that any nation, or political system I should say, that grants immunity to its all-powerful ruler, elected or not it makes no difference, while he holds the reins of power, is a global disgrace. It’s more or less the definition of a dictatorship. For example, he can’t be held to account if, while in office, he makes an executive decision to declare a state of emergency due to the massive corruption of all his enemies, and to abolish all federal elections forthwith.

Canto: A reductio ad absurdum perhaps, but one probably not far from the boy-king’s mind. In fact, the lad has been ‘joking’ about a third and fifth term. So people need that reductio kind of thinking to see what peril they’re in, seriously. And Judge Howell sees it clearly, as she reminds those who would read her that the boy and his playmates were found to have behaved very naughtily indeed, in a way that undermined the proper functioning of the state in multiple ways, long before the attempted extortion of the Ukrainian Prez.

Jacinta: Judge Howell argued, correctly, that a revisiting of the Mueller Report’s findings were in order for the purpose of deciding about these grand jury redactions. And so, she correctly reminded Americans that the Special Counsel found that links between the Putin dictatorship and the boy-prince’s pre-ascension team were ‘numerous’, and of course there was the Ukraine-Manafort nexus, which is mixed up currently with the lad’s most recent peccadillos. In fact, Her Honour helpfully points out that the then princeling likely knew about Dictator Putin’s assistance toward his ascension, by quoting from the Report:

Manafort, for his part, told the Office that, shortly after WikiLeaks’s July 22 release, Manafort also spoke with candidate Trump [redacted]. Manafort also [redacted] wanted to be kept apprised of any developments with WikiLeaks and separately told Gates to keep in touch [redacted] about future WikiLeaks releases.

According to Gates, by the late summer of 2016, the Trump campaign was planning a press strategy, a communications campaign, and messaging based on the possible release of Clinton emails by Wikileaks. [Redacted] while Trump and Gates were driving to LaGuardia Airport. [Redacted], shortly after the call candidate Trump told Gates that more releases of damaging information would be coming.

Canto: Yes, those redactions seem to indicate that the then princeling and his courtiers knew about, encouraged and accepted foreign interference – hardly surprising news, but under the USA’s highly-worshipped Constitution that there’s a rootin-tootin High Crime and Mister Demenour.

Jacinta: But it doesn’t matter because the boy-king has absolute power and can do whatever he likes, he done said it hisself. And apparently there are some powerful American folks, apart from his courtiers, that pretty much agree. The King just has too many responsibilities to be interfered with while in office by such petty matters as criminal charges – which is a pretty obvious problemo, as the King can simply increase his duties, and make them permanent, in order to make himself more immune, for a lifetime.

Canto: So Judge Howell looked at this too, because this apparent immunity hangs by the slender thread of a view held by the DOJ ‘Office of Legal Counsel’ (OLC). Her Honour quotes from the Mueller Report, and adds her own very interesting comments:

“Given the role of the Special Counsel as an attorney in the Department of Justice and the framework of the Special Counsel regulations,” the Special Counsel “accepted” the DOJ Office of Legal Counsel’s (“OLC”) legal conclusion that “‘the indictment or criminal prosecution of a sitting President would impermissibly undermine the capacity of the executive branch to perform its constitutionally assigned functions’ in violation of ‘the constitutional separation of powers.’” …. This OLC legal conclusion has never been adopted, sanctioned, or in any way approved by a court. 

What I suspect Judge Howell as saying here is, ‘it’s about time a proper court got hold of this OLC ‘legal conclusion’ and subjected it to the proper legal scrutiny it deserves, or very much needs.

Jacinta: She’s also happy to use the term ‘stonewalling’ in describing the DOJ ‘s tactics with regard to these redactions, a stonewalling that continues to this day.

Canto: Yes, and it’ll be interesting to observe the fate of Billy Barr, a principal toadie of the boy-king and Grand Marquis of the DOJ, as these adventures in Toyland play out.

Jacinta: So, overall, Judge Howell’s pretty contemptuous of the DOJ arguments, which she would prefer to call “arguments”, and has been extremely diligent in refuting them from every possible perspective she can think of, with a lot of case law and something of a history lesson regarding the thoughts of James Madison, Alexander Hamilton and others. I’m thinking that not only will we have to bone up on US Federal law (and a lot of other law), we’ll have to read the whole of the US Constitution and the Federalist Papers to get more thrills out of watching this battle between the boy-king and the Constitutionalists (if that’s what it is) play out.

Canto: Yes, and I’ll be even more interested in the aftermath, after the bodies are buried and the blood has been wiped away. Will Americans still want to say that their quasi-dictatorial political system is the greatest in the known universe?

Jacinta: You betcha.

first volume of a collection of papers on the US Constitution, by Alexander Hamilton, James Madison and John Jay, quoted in Judge Howell’s decision

References

Click to access grand.jury.release.opinion.pdf

http://grandjuryresistance.org/grandjuries.html

http://theconversation.com/only-in-america-why-australia-is-right-not-to-have-grand-juries-34695

Written by stewart henderson

November 4, 2019 at 2:14 pm