We said Base Pair editing would outshine CRISPR. This breakthrough proves we were wrong. Or not

When is CRISPR- Cas-9 Base Pair Editing, and when is Base Pair editing CRISPR Cas-9?. Readers of this blog may be forgiven for thinking Base Pair Editing was the exciting new kid in town that was going to make CRISPR look like VHS tapes ( what they?–ed) But according to reports of a recent breakthrough in medicine, they are, sort of, one and the same thing.

Perhaps we had better start with the breakthrough. Doctors in Pennsylvania in the USA have used gene editing techniques to treat a poor little boy whose liver lacked the necessary enzyme system to process ammonia. Our reports come firstly from Ian Sample of the Guardian and the New England Journal of medicine via hyperlink) , where Base Pair is very much to the fore While Nature Briefing has the following take , again with the hyperlink to the NEJM, Baby Boy Receives CRISPR for One Therapy

A baby boy with a devastating genetic disease is thriving after becoming the first known person to receive a bespoke, CRISPR therapy-for-one. KJ Muldoon, now almost 10 months old, received three doses of a gene-editing treatment designed to repair his specific disease-causing mutation, which impaired his body’s ability to process protein. While Muldoon appears healthy, it is too soon to use the word “cure”, says paediatrician Rebecca Ahrens-Nicklas. “This is still really early days.”Nature | 5 min read
Reference: New England Journal of Medicine paper

From all of which we have obtain the following Learning Points for your Edification , gentle reader:

1 It matters less what you call it, and more that it works-the kid’s OK now!

2 Maybe Base Pair Editing is a subset of CRISPR the way that Hammersmith is a region of London. OK, it’s Hammersmith. But it’s London too. What’s the big deal?

3 It would be interesting to learn if other big cities like New York or Madrid for examples, contain smaller areas with funny names. But we will leave that to another day.

4 If you educate people, teach them critical thinking skills and give them some money to buy test tubes with, things like this can happen

5 If you keep people working long hours for little money, educate them to a minimum and give them things like Fox News to watch, societal outcomes may be very different

[1]https://www.theguardian.com/science/2025/may/15/us-doctors-rewrite-dna-of-infant-with-severe-genetic-disorder-in-medical-first?CMP=Share_iOSApp_Other

also: see LSS 23 7 2022 and follow ups

#gene therapies #base pair editing #CRISPR Cas-9 #medicine #health

What is Autism, anyway?

“Everyone is a little bit autistic”. A view you hear quite often. And for us, rather comprehensively dealt with by Dr Aimee Grant of The Conversation [1] The phrase means that all of us show some behaviours(a liking for routine, for example) which are present to a much higher degree in neurodivergent people. Ergo, we don’t have to put in the hard yards of research and thinking which this fascinating condition really invites. Wrong says Dr Grant. Autism is a defined neurological condition with clinical boundaries. Herself autistic, we think she knows what she’s talking about.

The idea of not pontificating on something you know nothing about (autism; and other things) is precious to us here. A few years ago there was a rather hysterical fuss among certain journalists that Autism was caused by the MMR vaccine. Cool heads and reasoned minds showed this idea to be incorrect. What we didn’t know then was that some of the cases that the advocates of the MMR theory cited in support of their cause may not have been autism at all. One of the cases may have been something called Rett syndrome as the acute mind of Professor Nessa Carey pointed out [2] No, we hadn’t heard of it either. So to help you, gentle readers to wade through this minefield of definitions, syndromes and human suffering, we thought we’d offer this brief guide to some of the other things that are out there, and manifest some symptoms which overlap strongly with autism. If only to show the utter, mind boggling complexity of what clinicians and others have to deal with.

Rett Syndrome Cause: Mutations on MECP2 gene Normal early development followed by regression. Mostly affects girls

Fragile X syndrome Mutation on FMR 1 Gene Not all fragile X persons are autistic. Not all autistic persons are fragile X

Phelan McDermaid Syndrome Deletion on chromosome 22, often in SHANK 3 gene

Social Communication Disorder Communication problems Does not involve repetitive behaviours typical of autism

Intellectual Disability(ID) with behavioural challenges cognitive delay is global; but many autistic people have above average intellectual ability

Sensory Processing Disorder (SPD) extreme sensitivity to stimuli e.g. light, touch, etc this is the closest to autism and it’s true many experts don’t differentiate it from autism

This is a tip of the iceberg, superficial treatment, as the bounds of our blog dictate. But it’s enough to make you pause and think “There are more things in heaven and earth than you have thought of in your philosophy, Horatio” as Hamlet once remarked. The real point is not what we know, but how much there still is to discover. And how those discoveries may yet be organised. But that’s a job for another day.

thanks to P Seymour

[1]https://theconversation.com/everyone-isnt-a-little-bit-autistic-heres-why-this-notion-is-harmful-256129?utm_medium=email&utm_campaign=Latest%20from%20The%20Co

[2] Nessa Carey La Revolution Epigenetica Biblioteca Buridan 2011 amazon completion point 19%

#autism #nessa carey #diagnosis #mmr vaccine #neurology #brain #genetics #behaviour #medicine #health

APPEAL: the charity that tries to mend broken lives like Peter Sullivan’s

It is November 1987. If you turn on the radio, you might hear T’Pau‘s popular ditty China in your Hand, or maybe George Michael belting out Faith. In the UK , Mrs Thatcher‘s government is reaching peaks of popularity, although last month’s financial crash is a harbinger of that there may be troubles ahead. But you don’t mind, because you’re going to see Cher in Moonstruck, and…….that’s it. Nothing else happens for 38 years. Because you are in prison. High Security prison in fact, for a murder which you did not commit. The world moves on, but you are frozen in 1987.

That’s what happened to Peter Sullivan. [1]His conviction was for the murder of a poor innocent woman called Diane Sindall, who died in tragically brutal circumstances in 1986, and whose real assailant has never been found. And despite repeated appeals to courts and organisations like the CCRC, whose ostensible purpose is to review purported miscarriages of justice, nothing was ever done, Until his case was taken up by APPEAL. They are a tiny charity, skeleton-staffed by lawyers and other professionals. Legal Davids taking on a Goliath of wrongful convictions. You can read more about their work here [2] One recent heart warming success was the release of an unfortunate man named Andy Malkinson who was wrongfully jailed for rape in 2003. Their are many other cases like his on our system; there will be in yours too, overseas readers.

We know there have been advances in Forensic Sciences. We know that Police Officers are forced to work far too hard, with dreadful lack of funds. We know that makes them vulnerable to all -too -human faults like jumping to conclusions and confirmation bias. ( we are less sympathetic to the hysterical vitriol poured out by the media when a “successful” conviction has been achieved) But we do know that the world needs an organisation that deals in the best currency of our species-second thoughts. APPEAL is one such. Hopelessly understaffed. desperately under resourced. They are there for every little person who has felt the full obdurate weight of the criminal justice system sitting right on their chests. And to help some of these victims stumble free, unbelievingly, into 2025.

[1]https://www.theguardian.com/law/2025/may/13/peter-sullivan-jail-murder-conviction-quashed-diane-sindall?CMP=Share_AndroidApp_Other

[2]https://appeal.org.uk/who-we-are/

here is their donate page, just to save you time (hint hint)

#APPEAL #CCRC #peter sullivan #diane sinda;; #andy malkinson #miscarriage of justice #court pf appeal #forensic science #dna

Cancer testing saves lives-and shows why science works

Today we a re going to talk about cancer. In the UK alone it kills 167 000 people annually, which is about 29% of all recorded deaths . Meanwhile about 3.5 million people are trying to live with it on a daily basis. The statistics for your country will be comparable, gentle reader. Nothing would cheer us more than to report some good news. And today we think we can, courtesy oft the far sighted Professor Peter Sasieni and his team at London’s Queen Mary University via the Mail [1] [2]

Professor Sasieni and his team are not pioneering cures directly. Their skill is devising new ways of testing. To detect the terrible disease early, before it can wreak havoc, and unleash the cures when they have the optimal chances of success. The linked article is a good summary of all the wonderful work they are doing. But we have filleted out this tiny quote which will give you some flavour of what they are achieving

Yearly screening under the fast tumour growth scenario led to a higher number of diagnoses than usual care – 370 more cancer signs were detected per year per 100,000 people screened. There were also 49 per cent fewer late-stage diagnoses and 21 per cent fewer deaths within five years than patients receiving usual care.

If that’s not hope we don’t know what is

But there’s a deeper story here. For us, the best working definition of intelligence is how you respond to reality. You may have a lot of money, talk well, and even have a genius IQ. But if you ignore facts, deny them, or distort them, then you are a fool. There’s no mystery about science. It is simply a way of collecting true facts and organising them according to the rules of logic, which is what Professor Sasieni has done. This works globally for things like changes in the climate. It works locally, for things like diseases in the human body such as a diagnosis of cancer To deny truth once is the start of denying it always. With fatal results.

[1]https://www.dailymail.co.uk/health/article-14694059/blood-tests-detect-earliest-signs-cancer-prevent-advanced-stage.html

[2]https://www.qmul.ac.uk/wiph/people/profiles/peter-sasieni.html

#cancer #testing #screening #health #medicine

Is Keir Starmer becoming a Socialist?

Because he’s certainly acting like one. Forget the labels that people apply to each other, and to themselves. They’re mostly rubbish anyway. Look at someone’s actions. Today, Sir Keir (great name, by the way) has announced that his government has announced major new controls on the flow of immigration into the United Kingdom.[1] In support of this action, he cites the social problems caused by uncontrolled immigration and the harm it does to the social fabric. In doing so he makes the classic socialist case for controlling the laws of supply and demand. The same argument that socialists of all kinds from the most milk-and-water Social Democrats way out to the crazed ravings of Maoists and Trots.

The Capitalist argument is quite different. The law of supply and demand is the best approximation we have to the way people live in groups. Any restriction of free movement of anything such as taxes, business regulation or migration controls is contrary to nature, and must therefore lead to long term harm. After all, what is more socialist than civil servants telling employers whom they may, and whom they may not, hire to do a job? The socialist riposte is clear: the State should ban your desire to hire foreign workers if by doing so you harm the well being of members of our community here.

No, we are not going to say which one we agree with. The capitalists had their time to run the world, particularly after 1991. Their dream of universal prosperity seemed to be a true busted flush after 2008. Since then, the wind has been blowing in a socialist, that is to say, regulated direction. Whether it is to be socialism of the National or International variety remains to be seen

[1]https://www.theguardian.com/politics/live/2025/may/12/immigration-keir-starmer-labour-reform-visa-foreign-workers-uk-politics-latest-live-news

#socialism #capitalism #sir Keir starmer #immigration #economics #politics

Is this plastic eating bacterium the ultimate in antibiotic resistance?

Bacteria that mutate to resist the strongest known antibiotics. At this blog, it’s in our DNA, if you will pardon the flippant quip. But-get this-what if the bacterium in question starts eating the walls you are trying to contain it in? Sounds fantastic, like the plot of one of those old 1950s B movies. Read this piece called Hospital Superbug eats Medical Plastic from the admirable Nature Briefings

Pseudomonas aeruginosa — a strain of bacterium that often causes antibiotic-resistant infections in hospitals — can produce an enzyme that can break down medical-grade plastic. Researchers found that the enzyme, dubbed Pap1, can break down a plastic called polycaprolactone that is commonly used in health care because of its biodegradable properties. The ability to break down plastic could explain why these microbes persist in hospital environments, says biomedical scientist and study co-author Ronan McCarthy.Nature | 4 min read
Reference: Cell Reports paper

We’ve put up the Cell Reports posting for you too here[1]in case the clicker above does not get you through

So is this it? The big one? A wave of highly infectious bacteria that not only eats us humans, but gleefully chomps its way through the very defensive systems we use use to contain it? Possibly, yes. But-let’s keep our Alans on, as they used to say in the old Guy Ritchie movies. For there are two good reasons to do so.

First, it’s only eating one type of plastic, so far. There are lots of others which could be deployed for special medical uses which will be less vulnerable.

Secondly, the fact that this plastic is indeed biodegradable, and that something has found a way to do it, offers great hope. Imagine a plastics ecosystem wherein every bottle, every carton, each piece of wrapping is open to attack by this Pap-1 enzyme. Potentially it opens the way to clean beaches, litter- free hedgerows and unblocked rivers and sewers. There is no reason that the genes to make the enzyme could not be spliced into a safer organism than Pseudomonas aeruginosa. It’s an ill wind that blows no one any good, we say.

[1]https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00421-8

#plastics #antibiotics #microbial antibiotic resistance #science #ecology #pollution

Friday Night Feast of Fun: VE day

The 80th anniversary of VE Day has bought an immense outpouring of celebrations. Millions who were not there will tell you how they long to put on a zoot suit and jive the night away to Vera Lynn, or roam the streets of London getting up to goodness knows what with perfect strangers on bomb sites (wasn’t it a bit cold?-ed)

But-how much would you have enjoyed it? For those who advocate free markets and liberal trade as the best cures for human ills, the Second World War makes very difficult reading indeed. The Government seized control of the nation’s food supplies in 1939,introducing an utterly comprehensive system of rationing, backed by bulk buying and ruthless imposition of standards. By VE Day on 8 May 1945 the nation was thinner, heathier, fitter and better fed that it had ever been before. Or would be ever again. But Civil Servants are not chefs, and the menus available on that famous date may seem very spartan indeed to the modern palate. We thought we’d offer the kinds of things which might have been served up. With the help,naturally, of one of the most likeable books in our collection: The Ration Book Diet [1] And follow it up with what you could drink.

First Course There isn’t one Both shipping and fuel were in short supply, making this stage a superfluous luxury. Now you know why they were so healthy. Wanna try it?

Main Course In their spring section, Brown et al suggest recipes for Kidney with Mustard and Madeira Gravy(p76) Vinegar and mustard baked chicken(p78) or broad beans with minted salsa verde (p80 ) Other things served up might have been Ham and pickle pie monkfish and bacon casserole or salad of some sort. Everything grown locally, or sourced form the nations own fields and fishing grounds. Should we go that way again?

Dessert They would probably have called it “afters” or “pudding”. Apricot compote , rhubarb bread pudding or rhubarb fool might have graced many a VE Day table . For treats as the night drew in: oatmeal scones. And that really is it. There were things about like spam, corned beef and even cheese(heavily on the ration) But you’ll have to read the book iof you want to know more about them.

Happy so far? Let’s pour a drink , or go to the pub

Popular beers of the day included Bass, Guinness and Trumans At home, these would have come in bottles. There were no fridges of course. The Ministry had strained every nerve to ensure the pubs were well stocked with much the same. We also found a cocktail list from a site called Bistrot Pierre. For us, the Gin Fizz stands out as an iconic component of the war-time vocabulary. At least from the films and TV programmes we’ve seen.

And wine? Oh come on. It all came from the continent, which had been under enemy occupation for four years. You had about as much chance of finding a mobile phone as bottle of chardonnay in London in 1945.

Still want to go there?

[1] The Ration Book Diet Mike Brown Carol Harris CJ Jackson The History Press 2010 https://www.amazon.co.uk/Ration-Book-Diet-C-Jackson/dp/1803993448

[2]https://www.bistrotpierre.co.uk/propeller/uploads/2020/04/VE-Day-cocktails.pdf

#food #drink #VE day #world war two #diet #health

Evolution is happening right now in South Korea

We tend to think of Evolution as something happening over millions of years. First, all those trilobites and early fish swimming in the warm Devonian seas. Then early newts and scorpions slithering out onto land, followed by dinosaurs and pterosaurs dodging the cycads; and finally those desperate battles between humans and mammoths in the frozen wastes of the tundra. Millions of years-billions if you look at things like bacteria and red algae.

But evolution isn’t like that. The change of one species into another is a by product some something much smaller, local and more rapid. It is about the environment selecting a gene here, now, for one small purpose. Read this from Nature Briefing, No Diver is an island

A tradition of diving on the South Korean island of Jeju might have influenced the genomes of all of the islanders. The Haenyeo — meaning ‘women of the sea’ — have been cold-water diving year-round and without any breathing apparatus for centuries. A genetic analysis revealed that gene variants associated with reduced blood pressure, cold water tolerance and red blood cell count — which is related to oxygen-carrying capacity — are more common in people from Jeju, regardless of whether they dive themselves, than in other South Koreans.CNN | 7 min read
Reference: Cell Reports paper

In other words, good old fashioned Darwin-Mendel natural selection of the central DNA of the organism. Because one gene variant conveys a selective advantage which the other allele doesn’t. Textbook case: on single genetic change will transform a bacterium into an antibiotic-resistant organism, with profound consequences millions. Of course, if you have enough of these over time, you might eventually transform a tabby into a tiger, or a dinosaur into a bird. But those are second order consequences.Recent discoveries have made our understanding a little more complicated. We have to factor in epigenetics (the great Nessa Carey is good guide [1] ) and even the possibility of some environmental feedback into the genome, to which we have alluded here sometimes(LSS passim)

Every so often we come across some fool, usually a pub bore or right wing columnist, who loudly declaims” I don’t believe in evolution-why would a fish want to transform itself into a salamander?” Here is your answer. The majestic old Darwinian model still functions, Right at the heart of one of the most modern countries in the world.[2]

[1]https://en.wikipedia.org/wiki/Nessa_Carey

[2]https://en.wikipedia.org/wiki/Haenyeo

#natural selection #evolution #epigenetics #darwin #mendel #dna #gene #south korea

A Quick Roundup: Power from rain, a plea for peace, Base Pair goes big, reality trumps Trump-and Schubert on hubris

So many stories have crossed our screen in the last few days that the only thing we could think of was to run a quick round up and invite you to dive in for yourselves

Pennies from Heaven? The desperate need for renewable sources of power can produce some surprising ideas. For once the old Bing Crosby number may come true as this intriguing idea of generating electricity from raindrops shows. Popular Mechanics has the story:

_{thanks to P Seymour}

India-Pakistan: please don’t do it! We are ignorant of the quarrel between these two great nations. But the consequences of a nuclear war would be dire indeed. Apart from the millions of dead and wounded, the unprecedented waves of refugees would find a chilly welcome wherever they went. They too would be breathing the clouds of radioactive waste(and goodness knows what other toxins) from the burning cities. And, we know this is unsayable, but we will anyway: the only real winner would be China, with no strong powers to counterweight it. We have many readers in the subcontinent: what have you got to gain? Alright, we go with the Mail: but as George Orwell noted, even they can be right sometimes

https://www.dailymail.co.uk/news/article-14686439/The-world-worried-tit-tat-strikes-hated-rivals-India-Pakistan-quickly-spiral-nuclear-Armageddon-countries

Base Pair Goes to market We have long sung the praises of new biochemical techniques like CRISPR Cas 9 and Base pair editing. But, we humbly admit, it’s always from a slightly academic, detached viewpoint. Some of our correspondents have a more hard-nosed commercial orientation. Which is why they sent us the exciting tale of companies taking it into real-world, commercial solutions

https://www.biospace.com/drug-development/safer-crispr-base-editing-breaks-through-in-the-clinic-as-beam-verve-advance?

_{thanks to G Herbert}

Donald Trump’s Cunning Plan won’t work Ever since February, a story has been drifting in and out of the financial columns; Donald Trump’s actions are all part of a Cunning Plan to crash the dollar and bring the rest of the world to its knees in Mar-a- Lago, where he will dictate terms as he pleases. It was scary, it was tempting to believe: but it relied on flawed assumptions as Kenneth Rogoff succinctly explains in this piece for the Grauniad (surely “Guardian?”-ed)

https://www.theguardian.com/business/2025/may/07/why-donald-trumps-plan-to-weaken-the-dollar-is-flawed

Schubert : the queasy air of Pride before a Fall Ever since Griffin Johnson, the armchair historian [1] used it to accompany the French Army marching to Sedan, Schuberts Piano Trio in E Flat, No2 has really put the hook in us. You know, that outward confidence masking deep ineer doubts. Listen to the second movement if you don’t believe us. And wonder what happens to over-confident politicians just as the pass their peak.

https://www.bing.com/videos/riverview/relatedvideo?&q=schubert+piano+trio&&mid=3A9911F1E9485D296FD63A9911F1E9485D296FD6&&FORM=VRDGAR

#donald trump #base pair editing #economics #CRISPR Cas 9 #india #pakistan #nuclear war #renewable energy

[1]https://armchairhistory.tv/en-gbp/

Cortical Labs: the first working Synthetic Biological Intelligence

Far back in the last century, Arthur C Clarke drew attention to a slow but steady trend in human evolution: the gradual merging of the human body with artificial technology. Like all great things it started small, so small as to be almost unremarked. Firstly were primitive artificial legs and hands, all that could be done with the technology of the time. By the time Clarke made his prediction in the novel 2001; a Space Odyssey, the scientists of the day were experimenting with artificial hearts, lungs and kidneys. Fast forward to our own age. Not only have things like prosthetic limbs and eyes greatly improved. We are starting, tentatively, to modify the genes of living cells with early techniques like CRISPR Cas-9 (LSS passim). Elsewhere, the attempts to engineer interfaces between human tissue and silicon chips seem to be showing real possibilities of success.

But we think that the efforts of Cortical Labs to create Synthetic Biological Intelligence(SBI) takes the trend to a whole new level. [1] Their CL1 computer uses laboratory grown neurons interfacing with silicon chips to create an entity that defies old -style classifications of what is biology and what is technology. Rather than offer you 18 dreary paragraphs, we will urge you to visit their website. But if we cherry-picked that: The CL 1 far more energy-efficient than a conventional computer; that it is ideal for disease modelling. drug disorder research; that it dispenses with much of the need for animal experiments; that above all it will be available for shipment at a cost of $35000, you would see why we have chosen this item for your entertainment today. Because we honestly thought that this kind of thing was decades away. Forgive us: but we have no financial, professional, personal or any other kind of relationship with this company. We never endorse; but when we report, we mean it.

And we do indeed report developments which seem to be genuinely game changing, and truly the work of the most intelligent people at the very limits of human accomplishment. We believe that this is one of them. Which is where our doubts creep in. For Arthur C Clarke also pointed out how the very act of adopting technology (stone tools at the beginning) transformed the biology of creatures that used it. So much so that they changed into new species, quite unrecognisable to their ancestors. And absolutely dependent on the new technologies to survive, with no possibility of de-inventing them . We are not the first to suggest that some engineered organism will replace us. But we do think that possibility is now very real and very near.

thanks to G Herbert

[1]https://corticallabs.com/cl1.html

#synthetic biological intelligence #cortical labs #artificial intelligence #computers #biology #evolution