Progress on Multiple Sclerosis: When Big Data meets Molecular Genetics

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Few of us have not met someone who is suffering from Multiple Sclerosis, that terrible wasting disease wherein the immune system seems to turn on its own body, especially in the fatty sheaths around the neurons. Leading to a progressive deterioration in mobility before confining victims finally to a wheelchair-or even worse. The experience for families and victims was extra-bad because for many years the cause seemed unknown, making hope of any cure quite unlikely. Michael Marshall of the New Scientist has been covering this story most assiduously. And so we are pleased to showcase it, because it celebrates achievements in two our our favourite fields-big data and molecular biology-and the benefits which accrue when scientists from both work together.

We urge you to read Michael’s article either by buying the hard copy mag (there’s tons else to read inside it) or paywalling past the link below [1] Suffice it to say: #1 The molecular evidence that the Epstein Barr virus (which can cause glandular fever) is involved. #2 That this has a strong effect on both B cells and T cells in the immune system, which ,when they go rogue, are essentially responsible for the terrible lesions of MS #3 That not all hosts of Epstein Barr virus go on to develop MS, because the chances of that depends on certain genetic propensities and variants and, best of all #4 the above and more, which we report so glibly, has been elucidated by the use of huge data studies : 10 million people in one, 617, 186 in another, even 471 000 B cells in another-how’s that for numbers, folks?-which were only possible because: #5 places like the UK and USA have worked to build big collaborative things the the UK Biobank and All of us. Well some of the people in those countries have anyway.

All of which leads us to few reflections, some of which will not be uncongenial to regular readers. Firstly, it seems a pretty good idea to spend money on science, especially basic research, instead of cutting it. Secondly scientists these days work best in large teams whose members come from all sorts of backgrounds and this is especially true when you throw multidisciplinarygroups of them together. And that this also seems to be true of football teams: how far would Arsenal FC. for example, have enjoyed their current success if they had insisted on retaining a staff entirely composed of plucky British lads? [2] The implications in turn for visa systems, cultural openness and plain common sense are clear in turn.

[1]Huge study reveals how Epstein-Barr virus may cause multiple sclerosis | New Scientist

[2]‘Everything can happen’: Trossard confident of Arsenal’s chances in final | Arsenal | The Guardian

#multiple sclerosis #Ebpstein-Barr virus #T cells #B cells #autoimmune disease #medicine #health

Hydrogen from Microbiology-another hopeful story from Nature Briefing

You might be forgiven for thinking we’re against bacteria at this blog. Got a beef with them, want more antibiotics to kill them, especially that pesky little Escherichia coli that is always clogging up the pristine pages of our little website. Nothing could be further from the truth: we are simply against bacteria that kill people, that’s all, and we admire the little creatures for all the useful things they do

Nothing more useful it seems than generating hydrogen in clean green ways that massively reduce greenhouse gas emissions. Of course we need hydrogen for all sorts of things-food, drugs, plastics-but the way it is currently made is depressingly energy intensive Which is what this remarkable team of researchers at Edinburgh University have done, re purposing E coli to make hydrogen in amazingly clean ways Get this extract from the admirable Nature Briefing:

. The new process involves growing a strain of Escherichia coli that naturally produces hydrogen when deprived of oxygen. The researchers added a palladium catalyst and substrate for the hydrogen to bind to, and when they removed oxygen, hydrogen was bound to 94% of the substrate.

And they didn’t stop there:

The team then turned waste bread into a food source that could be given to the bacteria instead of glucose, to show that this type of food waste can be repurposed. The system resulted in a three-fold decrease in greenhouse-gas equivalent emissions compared with using fossil fuels, according to the team’s modelling.

There’s a lot to be said here. First our admiration for the amazing work and intelligence of the scientists[2] whose original paper we seem for once to be able to reproduce in full. The marvellous ways old things like bread and E coli are recycled to useful purposes. And a further point which the team at the admirable Nature Briefing know well. Progress, hope even, comes from the application of the scientific method. The use of evidence and reason to judge it in that order. Nothing else, however much you might want it to be so.

[2] Native H2 pathways enable biocompatible hydrogenation of metabolic alkenes in bacteria | Nature Chemistry

#microbiology #palladium #greenhoiuse gas# hydrogen# E coli #sustainabilityn #drugs #plastics

WHO has a Cunning Plan to speed antibiotic development

“The scientific community has developed and approved new antibiotics in recent years. This is good, but unfortunately not sufficient to catch up with evolving drug-resistance bacteria, especially against those of greatest concern. We need a reliable pipeline with new antibacterial agents that are innovative, affordable, accessible to all those who need them.”

Dr Yvan Hutin, Director of Antimicrobial Resistance at WHO

Says it all really, everything that we’ve been banging on about here for the last six years and more. The problem is simple, but deadly. Although more than 90 new antibiotics are now in development, very of few of them target the really high-priority organisms that worry health care professionals: and even fewer of these are really innovative (in the way that penicillin was in its day for example) And so the World Health Organization, that most noble of entities has come up with a Cunning Plan to really get things moving. They gave divided it into three Target Product Profiles:

-our old friends the multidrug resistant gram negative bacteria such as enterobacteriales, Acinobacter baumanii and Pseudomonas aeruginosa, who’ve shown up in so many old LSS blogs we won’t bother to list them.

–Gram positives like Enterococcus faecium. We have wondered why the gram negatives have been getting all the attention, and seeing no Darwinian reason why the gram positives should not evolve resistance too, are extremely glad someone is at last paying attention to them.

-their third trope for action is bacterial meningitis, caused by organisms such as Neisseria meningitidis and Streptococcus pneumoniae among others. Particularly welcome, for of those who incur such dreadful infections, one out of six will die and of the survivors, about one in five will be left with some long term disimpairment.

Hats off to Dr Hutin in particular and the World Health Organization in general. The World Health Organization is often treated as a mere federation of its member states, but in practice it is something larger and more coherent than the sum of its parts. Individual nations see only their own budgets, their own pathogens, their own political cycles; the WHO sees the whole epidemiological chessboard. Its strength lies in that cooperative vantage point — the ability to gather data from Lagos and Lima, to convene experts from Seoul and Stockholm, and to turn a hundred local anxieties into a single, rational blueprint for global action. In a field as fragmented and under‑powered as antibiotic development, that kind of coordination isn’t bureaucracy; it’s civilisation defending itself. There’s your glass-raiser for Friday Night Cocktails, gentle readers.

WHO releases new target product profiles for urgently needed antibiotics

#antibiotics #penicillin #world health organisation #epidemiology #microbiology #health #medicine

When Bacteria Explode: a new clue in the old antibiotic arms race

Bacteria are relentlessly evolving resistance to our attacks with antibiotics and phages — but how? If we understood their tricks a little better, we might still have a chance of avoiding the lethal pandemics of antibiotic‑resistant organisms otherwise waiting in the wings. A new paper from researchers at the John Innes Centre[1] has now shed light on at least one way that whole populations of bacteria may be secretly defending themselves from our ministrations.

The team found that the bacterium Caulobacter crescentus has an extraordinary switch mechanism that can cause it to “explode” under certain conditions. When it does, it releases tiny virus‑like particles containing fragments of its own DNA. Pertinent to our quest, gentle reader, is that some of this DNA may include instructions on how to resist antibiotics — or perhaps even the bacteriophages we deploy against them. The researchers also identified the components of this switch, which go by the snappy names LypABC and CdxB. They don’t yet know exactly what flips the switch, but they have their suspicions.

All of this is good news for those of us following the antibiotic‑resistance story. We now have a clearer picture of how at least one type of bacterium spreads resistance among its own members. And if we know what these switches are, we have a fighting chance of intervening to turn them off. If, as the researchers suspect, the presence of a hostile phage is indeed one of the triggers, then this is a very great step forward indeed

[1]A bacterial CARD–NLR-like immune system controls the release of gene transfer agents

Emma J. Banks, Pavol Bárdy, Ngat T. Tran, Phuong M. Nguyen, Boris Stojilković, Kevin Gozzi, Abbas Maqbool & Tung B. K. Le Nature Microbiology (2026)C

[2]John Innes Centre | Excellence in plant science, genetics and microbiology

#antibiotic resistance #bacteria #dna #genes #virus #bacteriophage #health #medicine

Breakthrough for blindness, an old lesson re-learned: and a mystery question

Leber congenital amaurosis, called LCA for short, is the most common form inherited sight loss in children[1] It’s caused by defects in a cluster of genes including RPE65 and until recently was quite untreatable. Now, as Ian Sample reports for the Guardian,[2] a team of researchers have effected a major new treatment called Luxturna: a gene‑replacement therapy delivered by injecting a working copy of the RPE65 gene directly under the retina. By giving retinal cells the functional gene they’re missing, it restores the visual cycle and can improve light sensitivity, visual function, and navigation ability in people with RPE65-related Leber congenital amaurosis. Interestingly the team comprises a husband and wife called Jean Bennett and Albert Maguire who share the prestigious Breakthough Prize [3] with their colleague Katherine High.

Regular readers will share our admiration for the work of this remarkable trio. They may note moreover that the researchers have something else to teach us, something that strongly concurs with opinions often expressed in this blog:

Bennett said it was a “tremendously exciting time” for scientific and medical research, but warned that the US administration’s attacks on science could “cause damage for generations to come”, leading her to fear a brain drain that the country would struggle to recover from.

“Agendas have become politicised, government agencies that support basic and applied research have been undermined, knowledgeable advisers and experts have been dismissed or have fled and revised guidelines contradict decades of rigorous research,”

Says it all really. But don’t just sit around reading it here:tell your friends and neighbours. For us there still remains outstanding question. Is Albert Maguire by any chance a relation of Ken Maguire, one of the best pub landlords of the 1990s, being sometime manager of the superb Latymers in Hammersmith Road London W14?

[1]Leber congenital amaurosis – Moorfields Eye Hospital

[2]‘Oscar of science’ awarded to team behind gene therapy that restores lost vision | Science | The Guardian

[3]Breakthrough Prize – Wikipedia

#LCA #Blindness #gene therapy #medicine #health #science #research #pub #beer

Eyes show why evolution is never linear

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Opponents of evolution and natural selection are fond of quoting the eye as an example of irreducible complexity which they imagine will wash away all objections to their creeds: “How could anything so complex have evolved without a very clever chap like God being behind it?” they ask, “and why would it have evolved as it only works when it’s completed?” Aside from the logical error which astute readers will have spotted at once, the story of how eyes evolved not only demonstrates how it happened, but answers so many other questions,that it’s actually rather more interesting than the stories offered as an alternative. Read this beautifully explained article in the Conversation by George Kafetzis and Dan Nillson [1] for a full exposition. Our humble summary appears below.

About 620 million years ago there lived an animal that was ancestral to all animals that would ever have two sides and move forward. It needed to steer as it swam: so it had two light sensitive areas symmetrically up front on either side. Another patch on top told light from dark, and which way up it was. And there it might have ended except for two things One group of these animals went to live in the mud as filter feeders. Having no need to swim they lost the steering eyes. Of course they kept the middle eye as it as still important to know if the Sun was shining. But when some of their descendants in turn started swimming again they needed to steer. Slowly the sides of the top eye moved apart, developed lenses and became eyes. These were the vertebrates. And this is why the eyes of all vertebrates-fish, lizards, birds and humans are so very very different from all other animals :invertebrates, such as scorpions, flies, octopuses and so on . Never giving up moving, their ancestors needed those original bilateral side eyes which slowly became more and more complex. Look at a fly if you don’t believe us. For the record the vertebrates kept the third top eye, its just that in mammals it has shrunk to the internal pineal gland where it still controls lots of light-related things like sleep and melatonin release

Its funny to think of eyes starting simple, evolving, un-evolving in some groups, and then evolving again, all according to the needs of those animals at the time. Its refreshing to find our basic LSS beliefs confirmed. Truth, or knowledge worth knowing, is complex and requires a lot of patient exposition to tease out. And it shows that simple, this-explains-it -all tales only end up obfuscating any real understanding.l. Nice to think that what happened 600 million years ago still has lessons for us today.

[1]https://theconversation.com/our-modern-vision-evolved-from-an-ancient-one-eyed-worm-creature-278120?utm_medium=email&utm_ca

#evolution #natural selection #eye #cambrian #vertebrates #invertebrates #paleonto;ogy #biology

Beyond the Nation #5: what happens when the Big One hits?

No event is so unlikely that it won’t happen for certain. Statisticians (and insurers) have a name for this sort of thing: tail risks. Things which, although unlikely, would have catastrophic consequences. We’ve looked at a few before here (LSS passim); but by general consensus, the top six include: a sudden volcanic eruption (think Yellowstone or Campi Flegrei); an asteroid impact (think dinosaurs);a geomagnetic pole flip which would bring down all power, communication and navigation systems; a sudden solar flare which would do all of the proceeding and more; a gamma ray burst from a nearby star which would blow away the ozone layer: and a possible megatsunami caused perhaps by the collapse of the Cumbre Viejas formation in the island of La Palma in the Canary islands.

If you are going to plan for these things you want your plan to be optimal and your outcomes to have maximum success. You want your numbers of survivors to be as high as it could be, and your numbers of dead, injured, pandemic and starvation victims to be as low as you can get them. The problem is that catastrophes on a planetary scale expose a profound structural mismatch: the hazard is global, but the response will be fragmented. Each government plans for its own survival and has no incentive to think about its neighbours. In fact, it has no remit,so why should it? Yet if such an event did occur, the price will be paid in extra but wholly avoidable deaths, injuries epidemics and famines.

Ok, these events sit far out on the probability tails. Humanity has been lucky-for now. But we make a prediction: if such an event occurs the response of a planet organised into nation states will be far less effective than it otherwise would have been. Time will tell.

Coda: On completing this piece someone in the office suggested another and more likely catastrophe: the release of a deadly pathogen, such as engineered forms of bubonic plague, ebola or smallpox from a secret weapons laboratory. But that would mean a pandemic, gentle readers: and we are planning to deal with those in the next instalment of this series

#catastrophe #asteroid impact #tsunami #volcano #caldera #magnetic flip #solar flare

Quantum Computers model Quantum Matter

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Study this , Quantum simulations match real-world data. from the inimitable Nature Briefing. For you are seeing into the future, at a quantum level.

For the first time, physicists have matched detailed quantum-computer simulations to experimental data gathered from work with solid materials. Two teams of physicists achieved the feat independently: one simulated the physical properties of a magnetic material, such as its heat capacity, and the other modelled a different material’s response to being excited into a range of energy states. Both agreed with experimental data. The work “sets the stage for a new standard in the application of quantum simulation to materials science,” says theoretical physicist Daniel González-Cuadra.Nature | 5 min read
Reference: arXiv preprint 1 & preprint 2 (not peer reviewed)

And our thoughts? Well, for the first time, quantum computers have reproduced the real, experimentally measured behaviour of solid materials, not toy models or idealised systems. That matters because it turns quantum computing from a theoretical promise into a scientific instrument — one that can interrogate nature at its own level, rather than approximating it from above. It also signals that quantum tech is advancing faster and more quietly than the AI hype cycle suggests, edging into domains where classical intuition simply can’t follow. And in doing so, it blurs the old boundary between “understanding” and “emulating” reality, letting us use a human‑built quantum device to explore quantum structures our minds were never evolved to picture — all powered, in my case and yours, by nothing stronger than coffee.

LSS is about much more than antibiotics and Allosauruses, gentle readers. We do IT and computing too. If you want the real cutting edge stuff in many fields, all neatly wrapped up in espresso-sized cups, then this is where to place your order.

#IT #quantum computers #AI #materials science #sub atomic #technology #science

Ten years looking for new antibiotics: how are we doing?

How’s the campaign to get more antibiotics going?” We still sometimes get asked this in pub or supermarket. Not surprising really, after more than ten years on the job. And to answer that question we can think of no one better than the acute Julia Kollewe of the Guardian whose piece is as good a state-of- play message ( Pipeline of New Drugs to fight superbugs is “worryingly thin,” experts warn) as any we’ve seen for some time[1] So, what’s the score? How indeed is humanity meeting this existential challenge?

Not too well, actually. The bad news is that antibiotic resistant infections are still very much on the rise. More than 40% of known antibiotics lost potency between 2018 and 2023.[2] The number of antimicrobial projects run by big pharmaceutical companies has actually declined in the last five years. But you can read these and many other statistics from Julia and her linked organisations for yourself.

There are some bright spots: hats off to the UK’s GSK ,Japan’s Shionugi and Otsuka, and certain valiant American firms in California. But America’s real giant, Pfizer, seems to be falling off the pace-not surprising we think, given the political end cultural climate they now have to work in.

But for us Julia’s killer trope was to consult the learned Ara Darzi, an expert in cancer treatment. Who adduces the following gloomy thought:

New therapies mean cancer can be fought, “but then sadly patients succumb to an infection that was treatable a decade ago”, Lord Darzi said at the launch of the AMF report, adding: “You don’t win a game if you have three good strikers and your defence is weak.”

Cancer is indeed a deadly illness. And cures should be sought. But what’s the point if the poor patient dies three days later from an infection? That is why your interest in new antibiotics is still important, gentle reader: please keep supporting us.

[1] Pipeline of new drugs to fight superbugs is ‘worryingly thin’, experts warn | Pharmaceuticals industry | The Guardian

[2] Tools to fight AMR exist, but industry-wide action is needed to tilt the battle against superbugs | Access to Medicine

#antibiotic resistance #microbiology #health #medicine #drugs

VIR 5500: Promising new treatment for Prostate Cancer

Immunotherapy, which involves training the body’s own defence systems such as T-cells to attack cancerous tissues, has been one of the medical success stories of the last twenty years. Yet some cancers still demonstrate a certain recalcitrance in the face of the new ministrations. Unfortunately, one of them is Prostate cancer, the most common form of cancer in men, killing up to 1.5 million of them annually. But not only does this report by Nicola Davis of the Guardian [1] offer hope of real progress, it has some deeper lessons for those of us in the evidence-based thought-modulated community(EBTM). Which means you, gentle reader.

All immunotherapy depends on T Cell engagers (TCEs) which form a bridge between certain sites on the T Cell and on the tumour cell. Anyone working with them to try to cure prostate cancer encounters two difficulties. Generally, traditional TCEs can be pretty indiscriminate, leading to side issues like massive cytokine storms and problems with dose toxicity. Specifically, prostate cancer cells have a knack of resisting T cells, making immunotherapy especially hard to apply. Now a team led by the admirable Professor de Bono in collaboration with Vir Biotechnology[2] is trialling a new form of molecular cloaking treatment called VIR-5500 which masks the T-cells right up to the moment when they are in contact with the prostate cancer cells. A protease in the malign cells then activates the T-cells, unleashing their curative effect. We won’t spoil Nicola’s summary of the results, which you can read in her article. But you will find them impressive to say the least.

All of which goes to show what curiosity-driven basic science can achieve when money is spent on it. VIR -5500 could not have existed without decades of molecular immunology, protein engineering, tumour cytology and many other disciplines hidden away in unmanly places like university departments and research institutes. Which is ironic, because many of the butch types at the Dog and Duck, who routinely perform their masculinities by loudly decrying scientific research into things like climate change, will be the first to suffer when prostate cancer comes along. But History always teaches the same lesson to the deluded in the end.

[1] Researchers praise ‘stunning’ results of new prostate cancer treatment | Prostate cancer | The Guardian

[2] Our Strategy | Vir Biotechnology

#prostate cancer #immunotherapy #t cells #health #medicine #science #molecular biology