Antibiotic medicine, mitochondrial medicine, cancer medicine: three stories so good we couldn’t leave out any: and a deeper question for you

Three stories we saw this morning were so compelling that it was impossible to choose just one to showcase. Each was so novel, so rich, that they raised a deeper question: where do you stop? We could have spent hours digging into any of them. Instead, we’ll let you decide for yourselves, gentle readers, as we present each in turn — and return to that last question at the end.

Ancient Antibiotic Resistance

Our first story is a tour‑de‑force article in New Scientist by Joni Wildman. You may have already seen recent media reports about dormant bacteria in ancient sediments showing signs of antibiotic resistance. Well, Joni has the definitive deep dive for anyone who wants to understand what this really means. You’ll encounter plasmids, the resistome, and even how these discoveries might help us identify the antibiotics of the future. Her article is behind a paywall, but worth it — you get the rest of the magazine too. How ancient superbugs could help us fight antibiotic resistance | New Scientist

Joni’s article is behind a paywall, but worth it, as you’ll get the rest of the mag too

How ancient superbugs could help us fight antibiotic resistance | New Scientist

Mitochondrial Transfer? Confession: before we read this excellent article by Blake Forman for Technology Networks, we didn’t know very much about mitochondrial disease(actually our basic mitochondriology was a bit weak too) But it seems that some healthy cells may be able to donate their mitochondria, those busy little subcellular power stations, to neighbours with less healthy ones. What’s more, there are promising signs that this discovery may be translatable into practicable therapies, as Blake outlines in this extremely learned article.

https://www.technologynetworks.com/biopharma/news/healthy-cells-donate-mitochondria-in-potential-treatment-for-mitochondrial-disease-416832?fbclid=IwY2xjawUodV9leH

Infections and Cancer Well, this story by Zoe Hardy of the Mail really had to go in: a new study claims that on e in eight cancers may be caused by a previous infection. No, we weren’t expecting that one either. But Zoe’s sources (International Agency for Research on Cancer, Lancet Oncology) are impeccable, their data wide and deep, and the conclusions faintly unsettling. The usual suspects are in there-HPV, Hepatitis virus, EBV and of course poor public health and sanitation. Naturally more vaccination programmes would help-but that’s becoming an uphill battle in many places these days, isn’t it? Once more, read the article and judge for yourselves:

One in eight cancers are linked to infections, new study finds, including a common stomach bug linked to bowel cancer | Daily Mail Online

All of which leads us to our main point. Each of these stories begged more reading, more digging into the data and more pondering. But in the part of the universe where we live at least there are only 24 hours in any one day, and only seven of those days in your average week. So: where do you stop? Read too much on mitochondria and you won’t have any time for green aviation technology or research on cocktails. But skim over everything and we guarantee you’ll understand none of it. It’s a conundrum which we have never satisfactorily solved. How do you do it. Gentle reader? We’d love to know.

#superbugs #antibiotics #microbiology #joni Wildman #mitochondrial disease #cell biology #inherited disorders #blake forman #cancer #infection #vaccination #zoe hardy #public health

GutSee Health: pioneering therapies may help conserve precious antibiotics

Whatever else we write about, the problem of microbial antibiotic resistance, is still the raison d’etre of our humble little blog. So while we’re always on the look-out for stories about new antibiotics, new phage techniques, what have you, we sometimes cast our net a bit wider. To bring you news of techniques which, while currently aimed at other problems, offer us the hope that they may one day be relevant to the fight against antibiotic resistance. That thereby potentially help us eke out existing stocks of antibiotics, and maybe even buy us time to develop a few more. Morever, when the pioneer is one of those brave new companies we laud so often, then we are all the more eager. So today we are showcasing the work of UK based GutSee Health. Not because they currently work to replace antibiotics per se: but because they represent a way forward which we think one day might.[1]

At present Gutsee are working on treatments to contend with such intractable problems as Irritable Bowel Syndrome and Inflammatory Bowel Disease. At present these disorders are not primarily treated with antibiotics. But if you examine their website, you will discover the formidable expertise they are developing in applied Artificial Intelligence, microbiome engineering, and phage technologies. Techniques not to replace antibiotics: but to potentially reduce the need for them, thereby conserving them for another day. Look at this from their website, with special attention to the bit which we have emphasised:

…… we are building sophisticated machine learning models to decode phage–bacteria interactions and predict therapeutic responses. This enables us to design targeted interventions that remove harmful or pro-inflammatory microbes—whether in the gut or in wounds*—while preserving healthy ecosystems.

*our emphasis

Wounds, gentle readers. You know that’s where the danger of antibiotic resistance is real: and you know why. Industrial or military wounds are notoriously vulnerable to infection, and antibiotics have long been essential in managing them. But every surgical intervention is really the imposition of a wound, albeit in a good cause, whether to cure appendicitis, deliver a baby by caesarean, transplant a heart-or carry out another of the myriad medical processes which make our lives sustainable at all. We need every possible alternative we have to address these problems, because time is growing short. It is our prediction that the work of GutSee, and many heroic pioneers like them may have a very large role to play. We wish them every possible success.

Coda We couldn’t help thinking that the above is an advertisement for a high education, high pay economy with all the public infrastructure needed to support those things. But that’s for another sort of blog on another day.

# microbial antibiotic resistance #phage #AI #start up #Gutsee #irritable bowel syndrome #health #medicine #sugery #wounds

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

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

Progress on Multiple Sclerosis: When Big Data meets Molecular Genetics

Photo by Fayette Reynolds M.S. on Pexels.com

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

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

Humble little herb may have mighty role as antibiotic

Could a humble little wildflower growing unnoticed in bog and marshland be a key player in the science of antibiotic resistance? According to an article by researchers Ronan McCarthy John J. Walsh and Kavita Gadar for the Conversation[1], yes it could. For they have discovered that Tormentil (Potentilla erecta) [2] not only has intriguing antibiotic properties of its own, it may help us to retread and recycle some old human made antibiotics which are sadly reaching the end of their effective lives.

Tormentil has appeared for centuries in the herbariums of traditional folk medicine. It has been used variously to treat ailments as diverse as gum disease, diarrhoea and wounds. Noting this, our resourceful researchers put it into a cross study against 70 other plant species in their Laboratory. It came out tops, hacking into the biofilms that bacteria use to defend themselves and thereby shortening the lives of these creatures by more than somewhat. They even identified the active agents in the tormentil which are ellagic acid and agrimonem. But you probably guessed that, being such an erudite and well-informed bunch of readers. Even more remarkably they:

…. combined low levels of the antibiotic colistin – an antibiotic that is only used as a last-resort against severe infections due to its potential toxicity to patients – with the tormentil extract. The low-level antibiotic dosage wasn’t enough to kill the bacteria when used on its own. But when combined with the tormentil extract, the plant compound enhanced the antibiotic’s efficacy.

You don’t need to be an old LSS hand to realise our worries about the declining effectiveness of colistin and some of the other older antibiotics.[3]

And our conclusions? We’ve written over twenty blogs on the theme of antibiotics or other medicines which may be hidden in nature. And therefore to destroy wildlands in order to grow food which no one really needs, or to build shopping malls of aching vacuity, is biologically insane, whatever the short term economic benefits. That probably half of all wild plants contain something useful, if only to the secret services of certain well known governments . As Shakespeare had it

“Within the infant rind of this small flower / Poison hath residence and medicine power.”
— Romeo and Juliet, Act 2, Scene 3

[1] https://theconversation.com/wildflower-once-used-to-treat-wounds-and-sore-throats-shows-promise-in-fighting-dangerous-superbugs-279406?utm_mediu

[2] Potentilla erecta – Wikipedia

[3] Liu, Y.-Y. et al. (2016). “Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China.” The Lancet Infectious Diseases, 16(2), 161–168.
DOI: 10.1016/S1473-3099(15)00424-7

#health #medicine #antibiotic resistance #wild flowers #tormentil #bacteria #microbiology

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

Food: is it quite as good as you thought?

Food is everywhere these days. Shelves groan with glossy cookbooks, restaurants and gastropubs queue up for tax breaks, and the airwaves are thick with chirpy kitchen‑dwellers—some dropping their aitches with theatrical enthusiasm, others sounding as if they’ve just strolled out of a rowing club bar. Everywhere you look, there’s another beaming evangelist waving a saucepan and assuring us that their latest ‘blend’ is nothing short of a revelation. One could be forgiven for thinking that food itself has become a national moral project, a jolly good thing in which we are all expected to take an interest.

However the readers of our little blog being a thoughtful lot, we thought we’d put up two stories which might provide a little counter-balance to the general merriment. The first from the indefatigable Kat Lay of the Guardian (clearly she knows about more than just antibiotics) does not suggest food is bad per se. But it does suggest that being extremely careful about what you eat, and who is selling to you might be a very good idea[1] Her headline tells you exactly what we mean: Ultra-processed foods should be treated more like cigarettes than food – study

“OK, OK”. you say, “but wot I eat is my choice, innit, guvnor? If I ain’t doin’ no one else no ‘arm, wosser problem?” Well according to Nature Briefing, Eating Well is about more than your health, this might be:

Debates over what to eat — more protein, say, or less ultra-processed food — often neglect any mention of how our food systems affect the biosphere that keeps us alive. But nutrition doesn’t exist in a vacuum, notes Earth-systems scientist Johan Rockström. He co-chaired the latest update to the Planetary Health Diet, which aims to optimize human health globally and reduce environmental and social harms. It notes that “global greenhouse-gas emissions could be cut by 20% by 2050 by eating healthily, reducing food waste and adopting sustainable production practices”, writes Rockström. “If diets remain unchanged, however, emissions will increase by 33%.”Nature | 7 min read
Reference: The EAT-Lancet Commission on healthy, sustainable, and just food systems report

We want humanity to survive, really we do. If you went extinct there would be no one to man the check out tills at supermarkets and we’d have to use those ghastly check-out-yourself tills that are so slow, complicated and inconvenient. Yeah food is alright, sometimes. But as the old saying goes-be careful what you wish for.

[1]https://www.theguardian.com/global-development/2026/feb/03/public-health-ultra-processed-foods-regulation-cigarettes-addiction-nutrition

#food #nutrition #climate change #obesity #health #fat #protein #fast food #processed food

Can Cancer really save you from Alzheimer’s? Some great research, but also some caveats

Could having cancer really protect you from Alzheimers? For years epidemiologists have noticed that people who have had cancer — especially certain solid tumours — seem to have a reduced statistical risk of developing Alzheimer’s, but the mechanisms have been unclear. Now an exciting mew study suggests a possible explanation. Some cancer cells overproduce a protein called Cystatin C. This enters the brain where it interacts with the amyloid-β plaques which many researchers associate with the development of Alzheimer’s. Now, we can’t do better than put you onto Nature Briefing Why Cancer and Alzheimer’s don’t mix. and their admirable analysis of a paper that originally appeared in then Journal Cell. It contains all the links and primary source matter you will need. But we’ll make a couple of observations( see below); for that is our wont.

Cystatin C, a protein produced by cancer cells, could partially explain why people who have had cancer have a lower risk of Alzheimer’s disease. In a study in mice, researchers found that the protein can infiltrate the brain and bind to the molecules that make up the hallmark brain plaques of Alzheimer’s disease. This interaction draws the attention of immune cells, which then degrade the plaques. If confirmed in humans, the findings could suggest a path toward new therapies for Alzheimer’s, says cancer researcher Jeanne Mandelblatt. Nature | 5 min read
Reference: Cell paper

Firstly the research is obviously tip-top and exciting- regular readers will know our love of an unexpected truth hiding in plain sight . There’s potential here for some really radical treatments for Alzheimer’s and goodness knows what other neurological conditions. However: so far, the work only pertains to mice. That’s usual: but as it scales up to humans, there’s many a slip ‘twixt cup and lip as the old adage would have it. What’s more, the relationship between cancer and Alzheimer’s is complex and multifactorial — immune system changes, metabolic shifts, treatment effects and environmental and epigenetic factors may all have their say. And Cystatin C itself has been implicated in both protective and harmful processes in the brain, depending on context.

And there is a deeper problem which has nothing to do with the earnest efforts of the researchers but everything to do with the less than acute hominins who surround them and who will read about this in popular daily newspapers and in mediabytes on dubious feeds. Ever prone to believe stories rather than weigh evidence some will conclude that “ a cure for Alzheimer’s has been found!” Others will ignore the old warnings of the logic teachers, ever suspicious of over hasty correlation between cause and effect. Yes, this is exciting research, But cautious people will expect no life changing applications any time soon.

#Cystatin C #cancer #alzheimer’s #neurology #brain #health #medicine