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

Photo by Alejandro Quintanar on Pexels.com

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

IsoDDE: mixed-race love child of Biology and Information Science has a great future

One of the most exciting stories we have followed at this blog is the way new AI systems are suddenly speeding up the production of new drugs and other biological molecules (see LSS 1 12 20 et al) This week has seen another exciting step in the form of a new AI tool from Isomorphic labs. Read this piece, Drug discovery AI is akin to Alpha Fold 4 from Nature Briefing

Isomorphic Labs — a biopharmaceutical spin-off of Google DeepMind — has unveiled a new, powerful artificial-intelligence tool for predicting how proteins interact with drugs. The tool, called IsoDDE, can outperform other AI systems such as the open-source Boltz-2 and physics-based methods at determining binding affinity between a protein and potential drug. These skills have impressed scientists, but they highlight that IsoDDE is proprietary, and the technical paper that accompanied its announcement offers scant insight into how to achieve similar results.

Nature | 5 min read

The research and development of new drugs is one of the most arduous tasks that befalls the intelligent community. The central problem is pretty simple: how do you get your marvellous new drug to stick to a protein, and make the whole thing work the way you want it to? Proteins are not hard rigid statues of marble: they are soft, spongy and change shape in unpredictable ways when you put a new drug up against them. That’s the gap in function into which all that time, money and thought disappears. In theory new AI tools like Iso DDE (and others on the way no doubt) should rapidly speed the whole process by predicting myriad of possible shape changes as the molecular systems are brought together.[2] Moreover, to predict new bits on the target protein which we hadn’t thought of, where the drug might be made to stick to, And possibly, to crunch the numbers around all those new bits of protein, polypeptide and other molecules which are thrown up in the research process, to see if they have any likely uses as well. When we were young, Information Science and Biology were completely different disciplines with different faculties, buildings and career paths. It’s funny to watch them coming together so fructiferously, to produce such exciting offspring

[2]https://storage.googleapis.com/isomorphiclabs-website-public-artifacts/isodde_technical_report.pdf

#drugs #medicines #researh #AI #biology #health

Can your cat save you from cancer?

Cats: our feline friends: variously cute, lovable, admirable and beautiful. They’re becoming more and popular as pets. Which brings several advantages in the treatment of cancer, believe it or not. Like dogs, their nearest rival, they are exposed to all the same molecular slings and arrows of everyday domestic life-cleaning products- foods, fuels, what have you-as we are. But we also share more genetic material with them then we do with our canine chums. Moreover cancer is rapidly becoming a major cause of mortality in middle aged to elderly cats just as it is to humans in that stage of. It’s a set up for ground breaking studies. And Miguel Ángel Criado for El País and Helen Briggs of the BBC have two excellent reports on a groundbreaking study which has done exactly that. (teaser: one of these links is in Spanish, and one in English-can you guess which?)

The study, co-led by the learned Dr Louise van der Weyden of the Wellcome-Sanger Institute is the first really large map of oncogenic(cancer related) aspects of the cat genome. It’s full of intriguing details, which you can read by clicking on the marvellous articles which we have hyperlinked. But we could not resist a tiny spoiler, concerning Dr Weyden’s discoveries around the gene FBXW7 , a tumour‑suppressor gene whose loss helps drive aggressive forms of human breast cancer. Intriguingly, the same gene is frequently mutated in feline tumours. This cross‑species echo suggests that cats and humans may share a conserved vulnerability in the FBXW7 pathway, making our kitties unexpected partners in understanding this cancer mechanism.

And the conclusion? We need to help cats to help us. You could give to a cancer charity [3] You could give to a cat charity[4] But knowing our readers to be generous types we have included sufficient hyperlinks for you to do both!

[1] El mayor mapa genético del cáncer de los gatos abre la puerta a tratamientos compartidos con humanos | Salud y bienestar | EL PAÍS

[2]https://www.bbc.co.uk/news/articles/cvg3n7j8xyqo?at_campaign_type=owned&at_link_type=web_link&at_format=link&at_ptr_name=facebook_page&at_link_origin=BBC_N

[3] https://www.cancerresearchuk.org/get-involved/donate?

[4] Cats Protection | UK’s Largest Cat Welfare Charity

#cancer #breast cancer #cats #medicine #health #research #genome #oncology

How a frozen bacterium might stop the great ESKAPE

For microbiologists the great ESKAPE is not an old film on the telly at Christmas. It’s a classification of the six most deadly antibiotic resistant bacteria which they work with. These are of course: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.In other words, the bacteria that most effectively “escape” the effects of antibiotics, and thus sit at the heart of our current global antimicrobial‑resistance crisis. Now hope that they might be controlled is emerging from the icy caves of the Carpathian Mountains. And you might be forgiven for thinking that at first sight it actually makes things worse.

Because frozen in the ancient soil of Carpathian caves lies a bacteria with the snappy name Psychrobacter SC65A.3 -and it’s no less than 5,500 years old. We we’ve got two covers for you today: one in Spanish from that excellent newspaper El País by Miguel Ángel Criado and one from the Mail by Shivali Best. Both wax eloquent on its dangers: it seems resistant to at least a dozen of the best-known antibiotics. But here’s the rub: the same evolutionary toughness which let it develop these remarkable powers of resistance has also let it develop remarkable powers as an enemy of other bacteria. Including many of those on our ESKAPE list.

The natural tendency of people is to look at the scary side of anything: and thereby jump to the worst possible conclusions. We know that our readers are the ones who suspend belief a little longer, and always look deeper. In the long run that’s the only type of thinking that will release us from the antibiotics resistance crisis. And many others

[1] Hallada una bacteria helada hace 5.000 años capaz de plantar cara a superpatógenos | Ciencia | EL PAÍS

[2] Prehistoric killer superbug discovered in 5,000-year-old ice is resistant to 10 modern antibiotics, study warns | Daily Mail Online

#antibiotic resistance #microbiology #medicine #health #bacteria #ESKAPE

GCSE Revision: why humans became extinct

The following is a specimen answer to a History examination question set for GCSE students of the species Homo emergens in the year 2126 (year 76 NSE of the New Species Epoch)

Discuss the extinction of our predecessor species Homo sapiens in the middle of the 21st century and its replacement by Homo emergens

The factors that led to the downfall Homo sapiens, sometimes called humans, were in fact biological. Their cognitive capacities were no longer able to match the complexity of the world which their own technology had created.

Homo sapiens emerged from a group of similar hominin species such as Homo erectus and Neanderthals. It had evolved a brain structure which gave it an edge in cognitive reasoning. This allowed it not only to drive its competitor hominins to extinction: it allowed it to become, briefly, the biologically and ecologically dominant life form on this planet. And to form huge interconnected networks of information, trade and energy exchange called “cities”. Yet the brains of these creatures had not evolved beyond those of their ancestors. Who were adapted for survival in small hostile competing groups. The neurological architecture which had been so adaptive for that period was utterly inadequate for the complicated world which had been created in the last century of their existence. These cognitive inadequacies included confirmation bias, the sunk cost fallacy, motivated reasoning and a tendency to divide quickly into mutually jealous hostile groups. The primitive institutions which this species evolved were therefore plagued by short term bias, institutional inertia and deep patterns of hierarchical loyalty which left them unable to adapt to the rapidly changing complexities in which they operated. And none of these cognitive failures could be overcome, because they were part of the inherited biological adaptations of the species.

Thus the complications of the late human era such as climate change, Artificial Intelligence and disease pandemics represented a new environment to which this species could no longer adapt. Instead of solutions they caused economic decline, political polarisation and eventually The Great Final War of 2046. The massive falls in human population and its reduction to technological impotence provided the ecological niche into which our own species, Homo emergens, was able to move. Our current thriving is due to the same superior intellectual capacity which had allowed H sapiens to exterminate Homo erectus: as it in turn had done to the preceding Australopithecines. It is a mark of our intelligence that we have not exterminated our own predecessors but have confined their remnants to zoological parks where they may continue to be objects of scientific study and public amusement. Their fate shows that no species can survive if it is not well adapted to its environment: a lesson our own would do well to learn.

_{copyright: EmergentEdge Specimen solutions 76: “we write ’em- you pass ’em!”}

#biology #evolution #extinction #cognitive bias #war #climate change