Intismeran:First successful Phase 3 trial for Personalised Vaccines

A 200X photomicrograph magnification of a direct by Centers for Disease Control and Prevention is licensed under CC-CC0 1.0

Vaccines have been the most successful tool in public health for over 150 years. But up to now they have been generic: each one is raised and designed against a specific disease-such as rabies, smallpox and more recently malaria. A new class of vaccine changes that logic entirely. These are individualised neoantigen vaccines, built from the unique mutations in each patient’s tumour. Today we highlight the first positive Phase 3 results for one of these, as reported by the BBC’s Joe McFadden. [1]

Intismeran is constructed from the mutational “fingerprint” of each patient’s melanoma — a bespoke mRNA vaccine rather than a one‑size‑fits‑all jab. In the Phase 3 INTerpath‑001 trial, jointly run by Merck and Moderna, 1,137 patients with completely resected stage IIB–IV melanoma were randomised to receive either Keytruda (Merck’s anti‑PD‑1 therapy) alone or Keytruda plus Intismeran.[2] [3] This is how Joe summarises the early results:

Early results show this new jab extended the length of time these patients were cancer free, but it’s unclear for how long, according to an announcement by the two firms.

Encouraging, we say: hats off to the companies and scientists involved. As for the wider reaction from the scientific community, it is positive indeed, but we’ll leave it to Joe to tell you about that

At this point we invoke our two favourite LSS tropes: caution and caveat. This is an early-days report: the work must now jump all the usual hoops of peer review, regulatory approval scaling and much more before any kind of routine clinical applications are possible. But there are many reasons to be optimistic, not just about Intismeran, but also certain wider preoccupations of ours. Firstly: some of the best research is done by that happy, hard to define network of companies, research institutes and académe, which has done so much to transform the human condition since the nineteenth century. Secondly, genetic engineering, which we follow avidly here, is in its infancy-this is quite different to our regular antibiotics theme, isn’t it? But most of all, if you want life to really get better, stop believing in what you want to believe and start believing in the scientific method.

[1] Vaccine breakthrough stops cancer returning in trial – BBC News

[2] Merck and Moderna Announce Phase 3 INTerpath-001 Trial of Intismeran Autogene Plus KEYTRUDA® Met Endpoints of Recurrence-Free Survival (RFS) and Distant Metastasis-Free Survival (DMFS) in Patients With Completely Resected Stage IIB-IV Melanoma

[3] Merck-Moderna cancer vax slows recurrence in ph. 3 trial

# Intismeran # Keytruda #melanoma #vaccine #mRNA #health #medicine #cancer #reseach #peer review

ULEZ success suggests progress works-sometimes

Remember the waves of fury and anger that swept over certain sections of the population when the London ULEZ zone was introduced.? Among many acts of lawlessness, cameras and signs were smashed and street calming flower planters torn up, all to a cascade of spittle-flecked rage online and in certain popular news outlets. For those not au fait with every aspect of London news, ULEZ is a set of mayoral restrictions on the more lethal forms of traffic pollution, such as nitrous oxides and PM _2.5 particles which was introduced in part in 2019 before subsequent extensions in 2021 and 2023.

Now news comes, from Smitha Mundasad of the BBC,[1] of the remarkable health benefits which have already accrued in the short time since the new scheme’s introduction. A five year study of 3400 children(that’s good numbers, folks) comparing London to Luton(less polluted, but with same mix) revealed

Scientists say they have been “stunned” by how quickly young children’s lungs began to recover and grow after …….. after the introduction of an Ultra Low Emission Zone (Ulez) in 2019 reduced emissions

Being good journalism, based on good science, Smitha points out that other factors must be considered as well. Of course: coping with complexity is what marks out this blog and its readers. But we know the ULEZ achievement to be remarkable nevertheless. And how much cleaner central London is looking these days![2]

Which brings us back to those on the other side who do not really do complexity. Their thought is fast, their opinion quickly formed, their conclusions firm. In this they reminded us of opponents of other episodes of social change: smoking bans in pubs leap to mind. But then we also recalled the angry opposition to seat belts; drink driving laws; clean air acts, child labour restrictions, slavery eradication…..all the way back to the same sort of people who opposed the abolition of gladiatorial games and beast hunting in Ancient Rome. Someone always sees the downside, don’t they?

Perhaps the common thread linking our opponents is not lack of education or indeed intelligence. Perhaps it is that they have made a bet that terrible things only happen to other people : so why should they care? This attitude may work for a while until it is applied to dealing with truly all encompassing phenomena such as antibiotic resistance , disease pandemics and global warming. At which point terrible things will happen to them too.

[1]https://www.bbc.co.uk/news/articles/c1l1r1zne1ro?at_link_origin=BBCNews&at_bbc_team=editorial&at_ptr_name=twitter&at_link_type=web_link&at_campaign_type=owned

[2]Health risks related to air pollution by transport categories and vehicle types: Comparison by mortality indicators – ScienceDirect

#ULEZ #clean air #traffic pollution #health #london #diesel #particulates #lung #slavery #gladiators #smoking #antibiotic resistance #global warming #pandemics

Are you missing out on red light? A lightbulb moment for Graham Lawton and the New Scientist

It’s a funny thing to be a progressive. We ‘re always prey to the Law of Unintended Consequences. For example, we rack our brains to replace all those nasty energy intensive incandescent bulbs with lovely low energy LEDs . And suddenly there’s a new problem. Is the new light from the LEDs missing something the old incandescents were giving us for free? Something that might, just might, have been good us?

Now we take this problem seriously because it is brought to us by no less than Graham Lawton of the New Scientist, a sure guarantee of intellectual probity. Quite rightly the magazine keeps Graham and all its top writers behind a pay wall, so once again we beg you to either take a sub, or buy the magazine. But the essence of Graham’s article is that the old incandescent lights, for all their dreadful shortcomings. were throwing out long wavelength infrared light, a bit more like the natural light you find when you go outdoors. Graham presents intriguing evidence that these wavelengths stimulate mitochondria to produce energy-carrying ATP (adenosine triphosphate) which production facilitates any number of health benefits, But you’ll have to read his article to find out what those are! Not only do the new LEDs chop out most of that infrared; but the new types of window glass actually reduce its natural ingress further. If you are sitting indoors under the dominance of blue‑weighted indoor light (from computer screens for example) you may be missing out on something rather good.

So how do we as Whigs, progressives, rationalists or whatever you want to call us, take all this? Intelligent readers will already see the other side jumping up and down with glee “See-orl dem (expletive deleted) sointissstss tryin ter cure (expletive deleted) global warmin’ wiv dem crap new bulbs, only making fings worse etc etc” In the same spirit as they disparage initiatives such as renewable energy technologies or health initiatives such as the London ULEZ zone (see next blog) Well, let’s concentrate on the rationalist word Rationalists know the world to be infinitely complex, not reducible to tabloid newspaper soundbites. Naturally every new initiative will have a cost benefit ratio(only children believe in pure unalloyed good) The new LED’s have undoubtedly brought immense benefits Only a pub philosopher would be dim enough to throw them away. But we know the tools of reason and evidence will deal with this problem as it did with the other one. That is what differentiates us.

[1] The shock revelation that light bulbs are wrecking your metabolism | New Scientist

#incandescent bulbs #LED #energy #sustainability #red light #infra red #health #medicine #lighting #ATP

Incurable cancers-don’t pick and choose your Science

Over the years we’ve enjoyed bringing you good‑news cancer stories. Only a fraction of what’s available in the wider media, of course, but we try to showcase the ones that matter. And we think you will agree, gentle readers, that the overall direction of travel has been encouraging. Immunotherapy, CAR‑T, genomic sequencing — these are just a few of the leaps and bounds of the last decade. Compared with the situation in 1996, or even 1966 when tobacco was almost de rigueur, you might reasonably feel a measure of satisfaction.

Except, of course, for the truly intractable and life‑wasting tumours that still hover over all our lives. Poised and ready to strike, like a swarm of sinister angels from hell.

Our personal list might include Triple Negative Breast Cancer (TNBC), pancreatic adenocarcinoma, glioblastoma, and certain forms of ovarian and liver cancer. This handy list from ScienceDirect offers an excellent jumping‑off point for anyone who wants to learn more. [1] At which point the Reflective Reader might conclude: “More research to be done.” And there’s the rub, as Shakespeare would have it.

For over those same ten years we have drifted into an age when Science, Research and Investigation are increasingly at a discount rather than a premium. Attacks on climate science, vaccination, and epidemiology are nothing new — but they have increased in fury and frequency, and have afforded licence to dispute the findings of any reasonable and learned experts. Recall the vitriol poured on economists who challenged the latest popular fads in constitutional or economic matters, or sociologists who advocate a more rational approach to any number of issues around crime, the family and poverty. For a broader survey of these attacks on the physical sciences in general, see this link to The Skeptical Inquirer.[2], although for the sociological and economic tropes we have alluded to you’ll have to look elsewhere.

But it is not the specific assaults on rationality that matter so much as the intellectual climate they create. Facts are selected, conclusions jumped to, and the passion is for triumph rather than knowledge. Research is a human, social phenomenon, and it is as sensitive to the social trends around it as winds are to a warming climate. Some people may feel they gain by refusing to reason. But they will pay a long price in untreatable cancers, incurable epidemics, and broken economies.

How to remind them they still have time to make a choice?

[1] The 10 deadliest cancers, and why there’s no cure | Live Science

[2] The Disturbing Attacks on Science | Skeptical Inquirer

# Triple Negative Breast Cancer # glioblastoma # CAR-T # alcohol # cannabis #health #medicine #Climate Science

More good news on designer phages-and why we think they’ll work

Last week, with the help of our doughty researchers, we published a small piece describing how Artificial Intelligence is being employed to design new generations of bacteriophages, some of which might be used to target antibiotic‑resistant bacteria (LSS 8.8.26). Hopeful, certainly — but intelligent readers will ask the old question: what’s the chance any of this will work anytime soon?

Well, you’ll be glad to know that human‑modified bacteriophages have already been in action, and successfully too, since the far‑off days of 2024. They weren’t using AI to design the phages then, merely modifying them using another LSS favourite: CRISPR‑Cas9 gene editing.

Our first trope concerns a report in The Lancet Microbe, a long but reasonably readable paper describing a safety and tolerability trial of SNIPR001 — a combination of four CRISPR–Cas‑equipped bacteriophages — in healthy human volunteers. Results were encouraging:

“SNIPR001 was safe and well tolerated in healthy participants, with signals suggesting targeted activity against E. coli, despite the absence of a statistically significant effect.”

Our second trope comes from the excellent Michael Le Page of New Scientist, who reports on the clinical use of the same SNIPR technology — not a trial in healthy volunteers, but in an actual patient. His piece, CRISPR‑armed phages help treat severe superbug infection, is unfortunately behind a paywall, but worth crossing. It tells the story of a 65‑year‑old man in California with a severe, antibiotic‑resistant E. coli infection whose condition markedly improved after receiving these engineered phages. The lesson is clear: artificially-modified phages can work.

Now, nobody is claiming miracle cures — not the authors of the paper, nor Michael, nor ourselves. But all of us, in our different ways, are pointing to extremely encouraging signs. And remember our original point: all of the above took place, before our famous AI‑designed bacteriophages have even gone into trial. What possibilities might open up when they are fully deployed?

[1] Safety, recovery, and pharmacodynamics of CRISPR–Cas therapeutic SNIPR001: a phase 1, randomised, double-blind, first-in-human, dose-escalation study – The Lancet Microbe

[2] CRISPR-armed phages help treat severe superbug infection | New Scientist

# Artificial Intelligence # bacteriophages # SNIPR001 # CRISPR‑Cas9 #antibiotic resistance #bacteria #microbiology #medicine #health

Why antibiotic resistance will be very bad news for your Grandchildren

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Despite our occasional diversions into such recondite fields as History and Economics, this is still front and centre an Antibiotics resistance blog, gentle readers. Which is why when an article as good as the one we’re showcasing today called Antibiotic Resistant bacteria increasingly leaving children vulnerable to common infections, global study finds by the inestimable Melissa Davey of the Guardian, we drop all else in its favour.

And it’s packed with goodies, it touches so many bases: if you’re antibiotics fan get a load of this:

There’s a whopping great survey of 82 countries: 106, 581 samples, over 22 years, all controlled by some of Australia’s most prestigious learned bodies. If that isn’t great statistics then you can call us David Spiegelhalter [2]

Several of this blog’s sinister old favourites such as Acinetobacter baumanii, Klebsiella have their usual run out-don’t you love ‘em?

There’s a forward prediction to 2035 which ought to make anyone pause for reflection.

Despite the efforts of brilliant journalists like Melissa, learned scientists of all stripes and even dare we say our own humble efforts, antibiotic resistance is still the ignored elephant in the room of ~~medical science.~~ Sorry we meant human existence. Yep, we meant it.

Talking of which, the all too human failings of poor diagnosis and over prescription, agricultural misuse and poor public health are driving our collective squandering of this precious, once only ever, resource.

The less discussed economic aspects are touched on. Get this: there is sometimes a reluctance to run trials on children and developing treatments for them can be less lucrative for pharmaceutical companies There’s yer problem, guvnor.

The usual hero organisations such as the WHO get a mention, and rightly so given the Herculean task they face.

And a sad, sad story about a lad called Harry whose brief life will be utterly dependent on the rest of us finally doing something about this common peril

If we were to present a class of Freshpersons with a jumping off point which summarises just about every trope in the antibiotics story, then this article would be our choice. Well done Melissa, And keep ‘em coming.

[1] https://www.theguardian.com/australia-news/2026/jul/21/antibiotic-resistant-bacteria-increasingly-leaving-children-vulnerable-to-common-infections-global-study-find

[2] David Spiegelhalter – Wikipedia

#antibiotic resistance #bacteria #microbiology #health #medicine #infection

Sepsis v antibiotics: the Doctor’s dangerous dilemma

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Anyone visiting the South Coast towns of England will know we have a huge sepsis awareness campaign on at the moment, as every ambulance you see is plastered with messages on the subject. And rightly so: sepsis is the cause of enormous suffering and mortality, not to mention its toll on NHS resources. Which is why today we are showcasing the NHS sepsis framework (published only yesterday, gentle readers-we sure do scoop ‘em these days!) [1]. because down in the appendix is a little section which impinges directly on the fons et origo of this whole humble blog: microbial resistance to antibiotics, as if you haven’t guessed already. Because sepsis affords the physician the most awful, excruciating, dilemma.

It’s one of those medical emergencies where every hour counts, truly. When bacteria invade the bloodstream and the immune system spirals out of control, doctors just can’t wait days for laboratory cultures. Broad spectrum antibiotics must be thrown in immediately, because delay will be truly deadly. Maybe it’s sepsis, maybe it isn’t: but the only logical decision at that stage is to assume that it is.

Thereby creating an acute paradox. Because prescribing the antibiotics exerts evolutionary pressure on the bacteria, increasing the strain’s likelihood of developing resistance. And as we know here (LSS passim) every unnecessary course of antibiotics puts the bacteria one step ahead. Modern medicine is trying to perform two contradictory tasks: treat, but avoid overtreatment So although the report puts it in the calm precise language of an official report, sepsis management and antimicrobial resistance must be seen as two sides of the same coin.

And our thoughts? Firstly, we are full of admiration for the medical staff who are dropped into this agonising situation, recognising that they possess levels of emotional and intellectual intelligence far beyond our own limited capacities. Secondly that to shout for “more antibiotics“ is cheap rhetoric, as it just begs the question. And we’re always doing it anyway. A more fruitful answer might lie in things like better DNA sequencing, molecular diagnostics and AI assisted decisions, all of which might better identify the invading pathogen more quickly. Thus opening the possibility of a bespoke antibiotic to be delivered to the right patient at the right time. Now that would be a creative step indeed.

[1] NHS England » Sepsis modern service framework

#antibiotic resistance #medicine #health #microbiology #bacteria #sepsis #treatment

We learn something new about cancer from a great website called The Scientist

One thing we value here is a well‑written science story that tells us something we didn’t know — and does so in a trustworthy, responsible way. Not the sensationalist, attention‑grabbing material that flashes across our screens all too often. So when our researchers came across Colorectal Cancer and Childhood Exposure to a Common Gut Bacterium by Laura Tran in The Scientist[1], we decided to look at the source itself, to see whether it deserves a place among the canon of science‑news providers we consider worthy of your attention, gentle readers.

As you might expect, The Scientist specialises in clear, sober reporting: across the biosciences, speaking very broadly. The style is terse and informative, closely aligned in spirit with the journals and institutions it covers. There’s a strong news section, a quarterly print magazine, topic‑based browsing, and a generous set of resources. Our test search — naturally, Antibiotics — produced several well‑illustrated, highly informative pieces.

If pressed, we’d say the ideal reader is intelligent, graduate or postgraduate, and probably working somewhere in the life sciences. But there is plenty here for teachers preparing a good science lesson too. Or even two.

Our verdict: not as bite‑sized as Nature Briefing, nor as magazine‑like as New Scientist, The Scientist nevertheless earns a worthy place alongside them as a provider of news and ideas for the educated and reasonable community (that’s us, gentle readers). And in an age when so much content is shaped for attention rather than understanding, that’s a very important thing indeed.

And having satisfied ourselves that The Scientist is indeed a sober and reliable chronicler of the biosciences, we can turn to the story that brought us there in the first place. It is a quietly important one: evidence that early‑life exposure to certain strains of that perfectly ordinary gut bacterium — Escherichia coli carrying a particular genetic island — may leave a mutational fingerprint that shows up years later in colorectal tumours. No melodrama, no scare‑stories, just the steady accumulation of data: mutational signatures, epidemiology, and the slow, careful work of linking mechanism to disease. This is exactly the sort of thing the scientific enterprise does well, and exactly the sort of thing we like to bring to your attention.

[1] https://www.the-scientist.com/childhood-exposure-to-bacterial-toxin-tied-to-early-onset-colorectal-cancer-72952?fbclid=IwY2xjawSxsvNleHRuA2FlbQIxMABicmlkETBVNUo0ekNo

#cancer #medicine #science #life science #research #laboratory #start up #biotechnology

CRISPR meets Epigenetics: a marriage made in Heaven

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a natural defence system found in bacteria, which scientists have turned into a programmable way to edit genes with extraordinary precision. In practice, it comprises two parts: a guide RNA that acts like a GPS to find the exact spot in DNA, and a Cas9 enzyme that acts like molecular scissors to cut the DNA. Once the DNA is cut, scientists can delete, fix, or replace genetic sequences inside a living cell. Our first Cover seems to have been over six years ago (LSS 23 11 20), since when we have noted a startling range practical applications from areas as diverse as horse breeding, and sickle cell medicine, to its relationship with blue sky techniques such as Base Pair editing, CART and programmable therapeutics (LSS passim).

How gratifying then to see CRISPR-based tools now partnered with epigenetics, that other old favourite of these humble pages! Once again the lead is taken by the indispensable Nature Briefing, now our go-to for all new things Scientific Their summary CRISPR’s next act: editing the epigenome tells you most of what you need to know. But some readers may well wish to click on the handy link too

A handful of start-up firms are testing therapies that target specific epigenetic markers — essentially chemical groups that sit on DNA and the proteins that it is wound around — to treat everything from high cholesterol to a rare muscular disorder. Changing these chemical markers can switch genes on or off. Some existing medications influence epigenetic markers, but these drugs act broadly and lack specificity. A new cadre of scientists has found ways to precisely alter the epigenetic signals that influence specific genes.

Nature | 15 min read

There is much here to gladden the hearts of all who believe in Reason and Learning. The technique seemingly so radical a few short years ago is not only becoming routine, it is embedding itself into the wider corpus of medical and scientific practice. Practicable applications are multiplying and the opportunities to reduce human and animal suffering are thereby multiplying. If anyone asks us “why do you take such an interest in the progress of the Arts, Sciences and Letters?” one answer we give is: because of things like this.

If you want to know more about epigenetics, or molecular biology in general, then we cannot do better than recommend the works of the great Professor Carey:

Carey, Nessa. The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance.London: Icon Books, 2011. New York: Columbia University Press, 2012. ISBN: 9781848312920 (Icon Books); 9780231530712 (Columbia UP).

Carey, Nessa. Hacking the Code of Life: How Gene Editing Will Rewrite Our Futures.London: Icon Books, 2019. New York: Columbia University Press, 2019. ISBN: 9781785784972 (Icon Books); 9780231549769 (Columbia UP).

#molecular biology #genetics #epigenetics #CRISPR Cas 9 #medicine #health #DNA #RNA

Gene Megacluster: a really big moment in antibiotic research

The idea of whole and unexpected possibilities in antibiotic research excites our highest hopes-and those of readers who have accompanied us on this journey for years. None more so than this report from Nature Briefing Gene Megacluster boosts antibiotic arsenal. We’ve set up their usual summary, plus links: and then we’ll try to answer a few of your questions as best we are able

A newly discovered gene ‘megacluster’ in Streptomyces bacteria enables them to produce a variety of potent antibiotic compounds. These compounds act as a multi-pronged offensive weapon against other species, with each targeting different stages of the bacterial metabolic process. It’s more difficult for bacteria to develop resistance to attacks that hit several targets, so the discovery could lead to the development of new antibiotics, experts say. The research has “discovered something new in a system so extensively studied — hidden in plain sight,” says medicinal chemist Mark Blaskovich

Nature | 4 min read
Reference: Nature paper

So, what is this gene megacluster? An unusual stretch of DNA in Streptomyces that encodes four distinct families of natural-product antibiotics, including: one compound entirely new to science, another never previously recognised as an antibiotic, and two known families deployed in a new coordinated fashion. Not a bad haul for one discovery, we think.

What does it do in Streptomyces? All four molecules target biotin (vitamin B7)—a universal cofactor required for growth, cell division, and metabolic enzyme function in most bacteria. They attack different points in the biotin pathway: production, uptake, use, and availability, aided by flanking streptavidin genes that bind up free biotin.

Why is this discovery genuinely new? Well , all sorts of reasons: here are a few of the best

–Co-location is unheard of: Antibiotic biosynthetic pathways are usually scattered across the genome. Here, four unrelated antibiotic families sit side-by-side, implying intentional evolutionary selection.

–Coordinated multi-antibiotic strategy: Natural antibiotics typically act alone. This cluster encodes a team of molecules that hit the same vulnerability from different angles—something not previously documented.

–Hidden in plain sight :Streptomyces genomes have been mined for decades, yet this megacluster was overlooked because genome-mining tools historically focused on single-product clusters. We love this bit, as regular readers will have already discerned

–It appears to be widespread. The megacluster is present across multiple Streptomyces species, suggesting an ancient, conserved strategy rather than a rare curiosity.

Could similar clusters exist in other organisms? Likely, yes. The discovery provides a road map for genome mining that looks for coordinated multi-pathway clusters, not just single biosynthetic islands Early research might do better to focus on procaryotes rather than eucaryotes-but who knows?

How could it help us to develop new antibiotics? This is the Big One for us , isn’t it? Lots of ways potentially, but as of late June 2026 three practical routes suggest themselves:

1. Direct development of the four biotin-targeting molecules. Because they attack different steps in the same essential pathway, they could be: used individually, combined as a cocktail, or engineered into hybrid molecules. Multi-target antibiotics are inherently harder for pathogens to resist. So that will teach them we’re serious this time.

2. Synthetic biology reconstruction. The megacluster’s architecture can be transplanted into: Streptomyces strains, E. coli or yeast expression systems, or modular cell-free platforms, permitting all sorts of scaling and production advantages

3. Drug discovery by analogy The discovery provides a template: look for clusters that coordinate attacks on other essential pathways (e.g., folate, isoprenoid synthesis, lipid II). Genome mining guided by this logic could uncover dozens of new multi-pronged antibiotic families.

4. Biotin-pathway inhibitors as a new class Biotin metabolism is conserved across many pathogens, including Gram-negatives—historically hard to target. These molecules could seed a new class of antibiotics that bypass existing resistance mechanisms

At this blog we tend to rate discoveries by the possibilities they open rather than the questions they answer. By that metric, this one is big indeed-and we think you’ll al agree with that.

#antibiotic research #antibiotic resistance #health #medicine #biotechnology #genetic engineering #research #bacteria