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Prioritizing and interpreting disease-associated genetic variants remains one of the greatest challenges in human genetics. Today, we’re thrilled to introduce AlphaGenome Atlas 🧬, a genome-wide platform providing precomputed predictions for the regulatory effects of all ~9 billion possible single-letter changes and >100M observed indels in the human genome. Here... is what Atlas delivers: 1. Variant Prioritization via AVI To prioritize variants, we developed the AlphaGenome Variant Impact (AVI) score. AVI predicts a unified score per variant, where higher values indicate greater disruption. It achieves state-of-the-art performance across diverse benchmarks. As a proof-of-concept with our collaborators at Broad Institute, AVI prioritized a deep-intronic variant in DNM1, helping solve a previously unexplained rare epileptic encephalopathy case by revealing a brain-specific cryptic splice site. 2. Multi-Layer Molecular Interpretation Variant prioritization is only half the battle; researchers also need to understand why a variant matters. Atlas decomposes variant effects across multiple interpretable layers: •Feature Attributions which decompose each variant’s score into specific biological modalities driving the impact. •Cell-Type Specificity: Precomputed predictions with AlphaGenome across hundreds of biosamples reveal the exact cellular context in which a variant acts. •Regulatory Grammar: Over 2,600 de novo DNA motifs (and >250B genome-wide instances) show when variants directly disrupt critical regulatory binding "words". Explore the resource: 🌐 Interactive browser & precomputed data: - 🎥 Video: - 📖 Blog: - 📄 Preprint:show more

Jun Cheng

1,631 subscribers

11,434 views • 6 days ago •via X (Twitter)

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10 Comments

Jun Cheng6 days ago

To make AlphaGenome Atlas even easier to use in computational biology workflows, we also built an AlphaGenome Agent Skill 🤖 Instead of writing custom query scripts or parsing raw tables, you can interact with AlphaGenome Atlas in natural language directly with Google Antigravity! 🤖👇

Jun Cheng6 days ago

A huge congratulations to the entire team and all our incredible collaborators! Sincere thanks as well to the open-source genomics community whose foundational tools helped make this work possible. We can’t wait to see the discoveries the community makes with AlphaGenome Atlas 🧬

AGTP6 days ago

The way AVI scores help prioritize variants is a game changer, and we actually went deeper on this here:

_6 days ago

could you please do more to cite the encode project. it appears most data was trained on it. thousands of academic labs contributed and are starving for grant funding and recognition.

Chang M. Yun6 days ago

Huge congratulations! Meaningful resource for the community & helping understand disease 👏

kurt meer6 days ago

Epic! Thank you!

อริยะ บิลก่อเด็ม6 days ago

The practical value of cybersecurity emerges when it solves clearly defined problems with measurable outcomes in high-risk industries.

Anshul Kundaje6 days ago

Congrats Jun! Great resource!

Jun Cheng6 days ago

Thanks Anshul, also thanks for all the tools developed from your lab!

Robin Roehm3 days ago

Precomputing an effect for every variant is a lot of work. How much of the atlas has real measurements behind it, and for the variants that don't, how do you tell when a prediction is trustworthy?

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🚨🚨🚨 Dutch Cancer Researcher and Erasmus Medical Centre Assc Prof Maarten Fornerod discusses DNA contamination in COVID Vaccines. ---------------------------- ...for last 35 years or so I've been working uh in the areas of molecular biology, gene expression, biology, cancer biology and recently in the last years, maybe last 10 years in the context of big data and computational biology... ...when we use genetic vaccines what we do essentially is we're making a complex intervention in a very complex system. It's impossible to predict what happens if you combine these two complex systems, and you get unpredictable effects. .. And the only way to go about this is to do genotoxic research, when you want to introduce a genetic medicine into a human being and that genetotic research has to be independent, it has to be double blind, has to be long lasting. AND ALL THESE HAVE NOT BEEN DONE WITH THE GENETIC CORONA VACCINES! if there's a vaccine, there's a little bit of DNA in there upon injection that is very, very rapidly degraded by the human body. However if it's protected and in a lipid nanoarticle it can very efficiently be transduced in the cell... I've been doing this this many, many times. This is called lipofection and it's a very efficient way to introduce DNA into a cell. ...Many people think that this is not possible. But I've been working in nuclear transport for many years, I think more than 10 years. So I've been exposed to a lot of molecular cell biology of nuclear cytoplasmic transport. And it's clear that the DNA can enter the nucleus. Now to make things worse, the mRNA vaccine doesn't stay in the arm but it's detected in , in all different organs including the reproductive system. And so partly this is based on animal models, of course we know from Michael Morz that he has detected uh the spike protein in brain, in the heart and it's for sure it's detected in the blood and even in breast milk. ..So there's NO DOUBT that this mRNA vaccine spreads widely in the human body. ..Now from a genetic point of view, there are possible consequences uh of this and the consequences could be a 1. long term disruption of cellular processes that could lead to disease. 2. there's a risk of insertional mutageenesis in somatic cells that can lead to cancer. 3. the insertion mutogenesis takes place in a germ cell which would be a hereditary burden uh on the human population. 4. And you could also think that these um DNAs, could transfect the microbiome and it could possibly lead to bacterial resistance. So these are all possible..the consequences of these genetic vaccines in my view, the shortcomings in this rollout of these vaccines were there was no genotoxic research performed at all. There was no safety studies, on carcinogenic potential of these vaccines. My personal opinion is that it's now not a question of whether, it will integrate in recipient's DNA, but how often it occurs... It's just a numbers game. If you do this in many cells, many persons it will no doubt integrate in cells in human recipients. So the question does it affect the human genome? I would say it probably, I think it most certainly does. And you see Kevin McKernan here and he represented ah a preliminary data where he detected a possible Pfizer DNA in colon cancer biopsy one year after vaccination.

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aussie17

126,273 views • 1 year ago

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SANTINO

54,154 views • 6 months ago

Self Attention by hand ✍️ ~ 9 steps walkthrough below Self-attention is what enables LLMs to understand context. How does it work? So I drew and calculated one entirely by hand. Goal: turn four 6D features into four 3D attention weighted features, filling in every cell yourself. = 1. Given = Four feature vectors, six dimensions each, one per position. = 2. Query, key, value = Let us multiply the features by WQ, WK and WV. Queries, keys and values all come out of the same four features, and that is what the word "self" is doing in self-attention. = 3. Prepare for MatMul = We copy the queries across the top and the transposed keys down the side. Lining the two up is half the work. = 4. MatMul = Let us multiply K transpose by Q. Every cell is the dot product of one key with one query, which we use as a matching score. That works because the dot product is the numerator of cosine similarity: it is how alike two vectors are, before anyone divides by their lengths. = 5. Scale = We divide by the square root of dk, the dimension of a key vector, here 3. Without it the scores grow with the dimension and a 64-wide head would swamp the softmax. To keep the page doable in pen, the drawing approximates dividing by root 3 with halving. = 6. e to the power = Let us raise e to the power of each score. This is the first half of softmax, and the drawing uses 3 in place of e, which is close enough to do in your head. = 7. Sum = We add up each column: 16, 6, 7 and 12. = 8. Normalize = Let us divide every cell by its column sum. That gives the attention weight matrix in yellow, and each of its four columns is now a probability distribution over the four positions. The decimals are nudged as they are rounded, so every column still sums to exactly 1. = 9. MatMul = We multiply the value vectors by those weights. Each output is a blend of all four values, mixed in the proportion the attention matrix just decided, and it goes to the position-wise feed forward network in the next layer: the FFN box at the bottom of the page. The outputs: Attention weights (A), by column = [.2, .6, 0, .2], [.2, .4, .2, .2], [.4, .2, 0, .4], [.1, .7, .1, .1] Attention weighted features (Z) = [8, 2, 6], [8, 4, 4], [16, 4, 2], [4, 2, 7] The takeaway: attention is a weighted average, and everything before step 9 exists to decide the weights. Compare every position with every other, turn the scores into one distribution per position, then blend. 💾 Save this post!

Self Attention by hand ✍️ ~ 9 steps walkthrough below Self-attention is what enables LLMs to understand context. How does it work? So I drew and calculated one entirely by hand. Goal: turn four 6D features into four 3D attention weighted features, filling in every cell yourself. = 1. Given = Four feature vectors, six dimensions each, one per position. = 2. Query, key, value = Let us multiply the features by WQ, WK and WV. Queries, keys and values all come out of the same four features, and that is what the word "self" is doing in self-attention. = 3. Prepare for MatMul = We copy the queries across the top and the transposed keys down the side. Lining the two up is half the work. = 4. MatMul = Let us multiply K transpose by Q. Every cell is the dot product of one key with one query, which we use as a matching score. That works because the dot product is the numerator of cosine similarity: it is how alike two vectors are, before anyone divides by their lengths. = 5. Scale = We divide by the square root of dk, the dimension of a key vector, here 3. Without it the scores grow with the dimension and a 64-wide head would swamp the softmax. To keep the page doable in pen, the drawing approximates dividing by root 3 with halving. = 6. e to the power = Let us raise e to the power of each score. This is the first half of softmax, and the drawing uses 3 in place of e, which is close enough to do in your head. = 7. Sum = We add up each column: 16, 6, 7 and 12. = 8. Normalize = Let us divide every cell by its column sum. That gives the attention weight matrix in yellow, and each of its four columns is now a probability distribution over the four positions. The decimals are nudged as they are rounded, so every column still sums to exactly 1. = 9. MatMul = We multiply the value vectors by those weights. Each output is a blend of all four values, mixed in the proportion the attention matrix just decided, and it goes to the position-wise feed forward network in the next layer: the FFN box at the bottom of the page. The outputs: Attention weights (A), by column = [.2, .6, 0, .2], [.2, .4, .2, .2], [.4, .2, 0, .4], [.1, .7, .1, .1] Attention weighted features (Z) = [8, 2, 6], [8, 4, 4], [16, 4, 2], [4, 2, 7] The takeaway: attention is a weighted average, and everything before step 9 exists to decide the weights. Compare every position with every other, turn the scores into one distribution per position, then blend. 💾 Save this post!

Tom Yeh

27,292 views • 1 month ago

"We have sequencing from a colon [tumor] biopsy from a patient who was 4 times vaccinated...we can find [DNA] plasmids in there a hundred copies per cell. They're not exactly the same as Pfizer's, which is a real head-scratcher, but they're in there." Kevin McKernan (Kevin McKernan), Chief Scientific Officer and Founder of Medicinal Genomics, as well as former R&D lead of the Human Genome Project, describes for Nick Jikomes (Nick Jikomes) how he and his colleagues have sequenced a colon tumor biopsy from a person who took four COVID injections and have found DNA plasmids—almost certainly from Pfizer's COVID-injection manufacturing process—at a ratio of 100 per cell. McKernan notes that the plasmids, however, are "not exactly the same as Pfizer's," which "is a real head-scratcher." "We haven't published the work yet, but we have sequencing from a colon biopsy from a patient who was 4 times vaccinated. A year after vaccination, they had a colon cancer. They biopsied it that day, and then 30 days later, they died, and then they biopsied after, and we have sequencing on both the pre-mortem and post-mortem samples," McKernan says. The scientist and entrepreneur, often cited as the first person to find DNA contamination in the mRNA COVID injections, adds, "we can find plasmids in there a hundred copies per cell. They're not exactly the same as Pfizer's, which is a real head-scratcher, but they're in there." "There's two of them," McKernan says of the plasmids. "And one encodes spike and one encodes nucleocapsid. We don't know where the hell the nucleocapsid one's coming from." (For reference, a nucleocapsid of a virus is the protein shell or capsid that encloses the nucleic acid—DNA or RNA—content, providing protection and structure to the viral genome.) When asked why the plasmids wouldn't exactly match those used in Pfizer's mRNA-injection manufacturing process, McKernan speculates: "Do they have more than one [DNA plasmid] in circulation? Like, BioNTech got a different manufacturing plasmid than the manufacturing plant out here in the US because they're making these in two different locations? It's possible. Is there contamination in their laboratory, in the manufacturing of this, they get the wrong plasmid in their E. coli vat, and suddenly they've got a different background there?" "And we've gotta do everything on our end to make sure we didn't introduce it, which we're doing. We're running all types of experiments to show that there's spike expression going on. But there's any number of reasons that could explain this," McKernan adds. Note that DNA plasmids—small, circular, double-stranded DNA molecules capable of replicating independently within a bacterial cell—were understood to be used in the manufacturing of the mRNA injections, but should've been removed below a certain threshold established by regulatory authorities such as the FDA. (The DNA contamination may be present in vials at 1,000 times higher than allowable according to one article published by the Brownstone Institute covering this issue. Article title: "The Vax-Gene Files: An Accidental Discovery") "We've got a case now that we're zeroing in on that looked like the SV40 poly-A signal, which is a termination signal. It's a transcription termination signal. We've got a piece of that integrating into chromosome 21, and it's breaking a gene that's involved in cancer. So, that one looks really interesting," McKernan tells Jikomes. "That could be maybe the driver of this whole thing. But the program spits out a long list of potential integrations that we have to go through and verify which ones are real and which ones are artifacts and all that. So I don't wanna get ahead of ourselves on that. That hasn't been Sanger verified yet." (For reference, Sanger sequencing is a method used to determine the precise order of nucleotides in a DNA molecule; the SV40 promoter is a strong regulatory region from the Simian Virus 40 that drives high levels of gene expression in mammalian cells when used in genetic constructs; a poly-A signal is a sequence in DNA or RNA that signals the end of a gene, prompting the addition of a polyadenine tail to the mRNA during processing, which stabilizes the mRNA and aids in its export from the nucleus.) "But the copy number alone suggests that these things aren't fully fragmented. Right? These plasmids really shouldn't be replicating to a hundred copies per cell," McKernan adds. "They couldn't, they shouldn't be in there at that level, because if you just do the math on how much is in the vaccine, when you do an injection of this, this person has four vaccines...1.2 ml of Pfizer...went into about 87,000 mls [of] body volume. So you should have a massive dilution into your body. Yet when we're sequencing this and doing qPCR off the tumor, the CTs coming back off the tumor are almost as high as they are straight out of the vial." (For reference, qPCR—or quantitative Polymerase Chain Reaction—is a technique used to amplify and simultaneously quantify a targeted DNA molecule. "CTs" is a reference to cycle threshold; PCR cycle threshold is the number of cycles at which the fluorescence signal from the reaction exceeds the background level, indicating that the target DNA amplification has occurred.) McKernan goes on to say: "And even if it were an integration event [that is, the DNA plasmid integrated into the genome]...I think there could be two things going on here: There could be plasmids replicating episomally [in the cell] and there could be parts of them integrated. But if it were purely integrated and the plasmid was gone, we would not expect to see the copy number of what integrated to be higher than the copy number of the genome. Right? You'd get one integration into one chromosome probably. So it would be half the signal of what you get amplifying a human house gene like RNAP, which is what we use. You would get a similar CT if it integrated. Because if it were a driver mutation, the cells would take off, and it would maybe have one copy of that mutation with it. And as a tumor advanced, you would probably you expect to see a CT score in PCR for that region that was similar to the actual genome background. But we're not seeing that. We're seeing CTs that are that are way ahead. If it's a hundred fold up there, it's around six to seven CTs ahead of the RNAP gene, which is the human gene. And then when we do sequencing, we see the same thing. "The coverage of sequencing is like 100 to 200X in the plasmids [vs.] 1X of the human genome. So they're in this tumor at really high levels. And that tells us that it has to be replicating. And this was a formalin fixed tissue. So it's not like we could sprinkle plasmids on it from our laboratory to contaminate that and have them be translationally active. Formalin is like this process when you take a tissue and you Formalin fix it. It's like...carbon freezing Han Solo. Alright? So you can't add plasmids after the fact and get it to replicate on cells, and you can't add plasmids on the fact afterwards and get it to integrate. Like those things can only occur if the cells are live. So we're pretty certain we've ruled out that, alright, this isn't coming from us. The anti-vaxxers aren't pouring plasmids on this to create a story. "This has certain biological signals that show this was present in the patient when they were alive. We don't know the source of it. They were four times vaccinated, and one of the vaccines that they used was one of the earliest vaccines from December 30th 2020."

"We have sequencing from a colon [tumor] biopsy from a patient who was 4 times vaccinated...we can find [DNA] plasmids in there a hundred copies per cell. They're not exactly the same as Pfizer's, which is a real head-scratcher, but they're in there." Kevin McKernan (Kevin McKernan), Chief Scientific Officer and Founder of Medicinal Genomics, as well as former R&D lead of the Human Genome Project, describes for Nick Jikomes (Nick Jikomes) how he and his colleagues have sequenced a colon tumor biopsy from a person who took four COVID injections and have found DNA plasmids—almost certainly from Pfizer's COVID-injection manufacturing process—at a ratio of 100 per cell. McKernan notes that the plasmids, however, are "not exactly the same as Pfizer's," which "is a real head-scratcher." "We haven't published the work yet, but we have sequencing from a colon biopsy from a patient who was 4 times vaccinated. A year after vaccination, they had a colon cancer. They biopsied it that day, and then 30 days later, they died, and then they biopsied after, and we have sequencing on both the pre-mortem and post-mortem samples," McKernan says. The scientist and entrepreneur, often cited as the first person to find DNA contamination in the mRNA COVID injections, adds, "we can find plasmids in there a hundred copies per cell. They're not exactly the same as Pfizer's, which is a real head-scratcher, but they're in there." "There's two of them," McKernan says of the plasmids. "And one encodes spike and one encodes nucleocapsid. We don't know where the hell the nucleocapsid one's coming from." (For reference, a nucleocapsid of a virus is the protein shell or capsid that encloses the nucleic acid—DNA or RNA—content, providing protection and structure to the viral genome.) When asked why the plasmids wouldn't exactly match those used in Pfizer's mRNA-injection manufacturing process, McKernan speculates: "Do they have more than one [DNA plasmid] in circulation? Like, BioNTech got a different manufacturing plasmid than the manufacturing plant out here in the US because they're making these in two different locations? It's possible. Is there contamination in their laboratory, in the manufacturing of this, they get the wrong plasmid in their E. coli vat, and suddenly they've got a different background there?" "And we've gotta do everything on our end to make sure we didn't introduce it, which we're doing. We're running all types of experiments to show that there's spike expression going on. But there's any number of reasons that could explain this," McKernan adds. Note that DNA plasmids—small, circular, double-stranded DNA molecules capable of replicating independently within a bacterial cell—were understood to be used in the manufacturing of the mRNA injections, but should've been removed below a certain threshold established by regulatory authorities such as the FDA. (The DNA contamination may be present in vials at 1,000 times higher than allowable according to one article published by the Brownstone Institute covering this issue. Article title: "The Vax-Gene Files: An Accidental Discovery") "We've got a case now that we're zeroing in on that looked like the SV40 poly-A signal, which is a termination signal. It's a transcription termination signal. We've got a piece of that integrating into chromosome 21, and it's breaking a gene that's involved in cancer. So, that one looks really interesting," McKernan tells Jikomes. "That could be maybe the driver of this whole thing. But the program spits out a long list of potential integrations that we have to go through and verify which ones are real and which ones are artifacts and all that. So I don't wanna get ahead of ourselves on that. That hasn't been Sanger verified yet." (For reference, Sanger sequencing is a method used to determine the precise order of nucleotides in a DNA molecule; the SV40 promoter is a strong regulatory region from the Simian Virus 40 that drives high levels of gene expression in mammalian cells when used in genetic constructs; a poly-A signal is a sequence in DNA or RNA that signals the end of a gene, prompting the addition of a polyadenine tail to the mRNA during processing, which stabilizes the mRNA and aids in its export from the nucleus.) "But the copy number alone suggests that these things aren't fully fragmented. Right? These plasmids really shouldn't be replicating to a hundred copies per cell," McKernan adds. "They couldn't, they shouldn't be in there at that level, because if you just do the math on how much is in the vaccine, when you do an injection of this, this person has four vaccines...1.2 ml of Pfizer...went into about 87,000 mls [of] body volume. So you should have a massive dilution into your body. Yet when we're sequencing this and doing qPCR off the tumor, the CTs coming back off the tumor are almost as high as they are straight out of the vial." (For reference, qPCR—or quantitative Polymerase Chain Reaction—is a technique used to amplify and simultaneously quantify a targeted DNA molecule. "CTs" is a reference to cycle threshold; PCR cycle threshold is the number of cycles at which the fluorescence signal from the reaction exceeds the background level, indicating that the target DNA amplification has occurred.) McKernan goes on to say: "And even if it were an integration event [that is, the DNA plasmid integrated into the genome]...I think there could be two things going on here: There could be plasmids replicating episomally [in the cell] and there could be parts of them integrated. But if it were purely integrated and the plasmid was gone, we would not expect to see the copy number of what integrated to be higher than the copy number of the genome. Right? You'd get one integration into one chromosome probably. So it would be half the signal of what you get amplifying a human house gene like RNAP, which is what we use. You would get a similar CT if it integrated. Because if it were a driver mutation, the cells would take off, and it would maybe have one copy of that mutation with it. And as a tumor advanced, you would probably you expect to see a CT score in PCR for that region that was similar to the actual genome background. But we're not seeing that. We're seeing CTs that are that are way ahead. If it's a hundred fold up there, it's around six to seven CTs ahead of the RNAP gene, which is the human gene. And then when we do sequencing, we see the same thing. "The coverage of sequencing is like 100 to 200X in the plasmids [vs.] 1X of the human genome. So they're in this tumor at really high levels. And that tells us that it has to be replicating. And this was a formalin fixed tissue. So it's not like we could sprinkle plasmids on it from our laboratory to contaminate that and have them be translationally active. Formalin is like this process when you take a tissue and you Formalin fix it. It's like...carbon freezing Han Solo. Alright? So you can't add plasmids after the fact and get it to replicate on cells, and you can't add plasmids on the fact afterwards and get it to integrate. Like those things can only occur if the cells are live. So we're pretty certain we've ruled out that, alright, this isn't coming from us. The anti-vaxxers aren't pouring plasmids on this to create a story. "This has certain biological signals that show this was present in the patient when they were alive. We don't know the source of it. They were four times vaccinated, and one of the vaccines that they used was one of the earliest vaccines from December 30th 2020."

Sense Receptor

335,167 views • 1 year ago

Single-cell technologies now let us profile entire transcriptomes in individual cells. But how do we make sense of this complexity in a biologically meaningful way? Many methods summarise cells into a single embedding, but this often comes at the cost of interpretability, especially when multiple gene programs are active at once. We developed Tripso, a self-supervised transformer model that represents cells through multiple gene program-specific embeddings, while also uncovering new programs directly from the data. Instead of collapsing biology into a single vector, Tripso decomposes cell state into multiple representations, each reflecting a different gene program. We explored this across multiple systems. In human hematopoiesis, spanning development to aging, Tripso identified distinct age-associated program activity, including stronger JAK-STAT signalling in early life and dynamic IKZF1-related changes during B cell maturation. By comparing in vitro culture conditions with in vivo hematopoietic stem cell states, Tripso suggested that targeting the SEC61 translocon could enhance stem cell maintenance ex vivo, a prediction that we subsequently validated experimentally. In parallel, we identified a previously uncharacterised tissue-resident memory T-cell program associated with atopic dermatitis and mapped it to distinct spatial immune niches Together, these results show how modelling cells through gene programs can lead to interpretable and experimentally testable insights. More broadly, this work points toward a more interpretable and biologically grounded models of cell state. As single-cell datasets continue to grow, we hope approaches like Tripso will help bridge the gap between data-driven representations and biological insight. This work wouldn’t have been possible without the contributions of an amazing team. Thank you to co-first authors Marie, Tomoya Isobe, Amirhosein Vahidi, Carlo Leonardi, and everyone from roser's Lab, Haniffa Lab, Nicola Wilson and Bertie Gottgens's Lab, bringing together expertise across Cambridge Stem Cell Institute, Open Targets, Wellcome Sanger Institute and Cambridge University. Marie is one of the very best PhD students I have ever supervised. She is truly a force of nature, exceptionally resourceful, deeply innovative, and one of the most impressive scientists I have worked with. I am immensely proud of her and all that she has accomplished. As she begins her internship at Genentech , I have no doubt she will do amazing work there and continue to make her mark. paper: code:

Mo Lotfollahi

22,525 views • 5 months ago

Welcome to the Lab of the Future! 🧬🤖 Excited to share LUMI-lab, out today in Cell — a self-driving platform that pairs an AI foundation model with a robotic lab to autonomously discover ionizable lipids (LNPs) for mRNA delivery. The core problem: Designing lipid nanoparticles (LNPs) is hard. The chemical space of ionizable lipids is vast, experimental cycles are slow, and — critically — historical LNP datasets are far too small to train a predictive model from scratch. Most AI approaches in this space hit a wall immediately: not enough data to learn from. Our solution: lab-in-the-loop foundation model learning. Instead of training on LNP data alone, LUMI starts as a transformer-based foundation model pretrained across broad chemical space, building rich molecular representations before it ever sees a single LNP experiment. Then it enters a closed loop with a robotic synthesis platform: predict → synthesize → assay → update. Each round of real wet-lab experiments fine-tunes the model, which then proposes smarter candidates for the next round. The lab isn't just validating AI predictions — it's actively teaching the model, continuously. What happened when we let it run: LUMI-lab autonomously synthesized and screened 1,700+ ionizable lipids in human bronchial epithelial cells. The top candidate — LUMI-6 — features a brominated lipid tail, a structural motif that had been largely overlooked in LNP design. LUMI found it without being told where to look. When formulated into LNPs and delivered intratracheally to mice, LUMI-6 achieved 20.3% gene editing efficiency in lung epithelial cells — a compelling result for one of the hardest-to-reach therapeutic targets, directly relevant to diseases like cystic fibrosis and alpha-1 antitrypsin deficiency. Why this matters beyond LNPs: This is a proof of concept for a broader thesis — that foundation model pretraining + active learning + robotic experimentation can overcome the data scarcity bottleneck that plagues AI-driven discovery in biology. You don't need a massive domain-specific dataset to start. You need a model that can generalize, a lab that can generate the right data, and a loop that connects them. Huge congratulations to first authors Yue Xu, Haotian Cui, and Kuan Pang, and to the entire Bowen LI team. Grateful to our collaborators at University Health Network and Leslie Dan Faculty of Pharmacy, and to Princess Margaret Cancer Centre Research Princess Margaret Cancer Centre Research. 📄 Paper:

Welcome to the Lab of the Future! 🧬🤖 Excited to share LUMI-lab, out today in Cell — a self-driving platform that pairs an AI foundation model with a robotic lab to autonomously discover ionizable lipids (LNPs) for mRNA delivery. The core problem: Designing lipid nanoparticles (LNPs) is hard. The chemical space of ionizable lipids is vast, experimental cycles are slow, and — critically — historical LNP datasets are far too small to train a predictive model from scratch. Most AI approaches in this space hit a wall immediately: not enough data to learn from. Our solution: lab-in-the-loop foundation model learning. Instead of training on LNP data alone, LUMI starts as a transformer-based foundation model pretrained across broad chemical space, building rich molecular representations before it ever sees a single LNP experiment. Then it enters a closed loop with a robotic synthesis platform: predict → synthesize → assay → update. Each round of real wet-lab experiments fine-tunes the model, which then proposes smarter candidates for the next round. The lab isn't just validating AI predictions — it's actively teaching the model, continuously. What happened when we let it run: LUMI-lab autonomously synthesized and screened 1,700+ ionizable lipids in human bronchial epithelial cells. The top candidate — LUMI-6 — features a brominated lipid tail, a structural motif that had been largely overlooked in LNP design. LUMI found it without being told where to look. When formulated into LNPs and delivered intratracheally to mice, LUMI-6 achieved 20.3% gene editing efficiency in lung epithelial cells — a compelling result for one of the hardest-to-reach therapeutic targets, directly relevant to diseases like cystic fibrosis and alpha-1 antitrypsin deficiency. Why this matters beyond LNPs: This is a proof of concept for a broader thesis — that foundation model pretraining + active learning + robotic experimentation can overcome the data scarcity bottleneck that plagues AI-driven discovery in biology. You don't need a massive domain-specific dataset to start. You need a model that can generalize, a lab that can generate the right data, and a loop that connects them. Huge congratulations to first authors Yue Xu, Haotian Cui, and Kuan Pang, and to the entire Bowen LI team. Grateful to our collaborators at University Health Network and Leslie Dan Faculty of Pharmacy, and to Princess Margaret Cancer Centre Research Princess Margaret Cancer Centre Research. 📄 Paper:

Bo Wang

57,510 views • 6 months ago

🇬🇧🇺🇸 #English - Biodigital Convergence and the Challenge to Free Will: A Critical Analysis by Dr. Geanina Hagima. In this presentation, Dr. Geanina Hagima conducts an exhaustive analysis of what she terms a "global attack on human rights" and the integrity of the human species. The content is broken down into the following fundamental pillars: * Denunciation of Undeclared Components: The doctor refers to findings by independent researchers (citing Lorena Diblasi and Marcela Sangorrín) regarding the presence of up to 55 undeclared elements in recent vaccination technologies. She contends that the use of nanotechnology and artificial intelligence in these products lacked the necessary regulation at the time of their implementation. * Cognitive Warfare and Neurotechnology: She presents the thesis that humanity is in the midst of a "cognitive war" that manipulates the subconscious through technological means. She explains how environmental particles and medical procedures could facilitate nanoparticles crossing the blood-brain barrier via the olfactory nerve, directly affecting neurological functions. * The Transhumanism Agenda: She links the objectives of Agenda 2030 with biodigital convergence, a process that seeks to transform the human being into a "transhuman" entity through the integration of biotechnology and information technology. She criticizes the visions of theorists like Ray Kurzweil, defending the perfection of natural creation against artificial "human enhancement." * Brain-Computer Interfaces (BCI): She warns about recent scientific publications presenting non-invasive interfaces capable of stimulating specific neuronal groups. According to her analysis, although presented as solutions for psychiatric diseases, these tools could be used for the remote control of the human mind. * Call to Action and Legislation: She concludes by emphasizing the urgency of creating legal frameworks that protect free will. She urges the medical community to investigate not only superficial biological effects but also the toxicology of new technologies, exhorting the population to inform themselves to defend the future of coming generations. The attached video shows a "new technology" developed by MIT (Massachusetts Institute of Technology) called "circulatronics," which consists of sub-cellular scale electronic devices that can be injected via a common syringe into the bloodstream. These microchips travel autonomously through the blood vessels until they reach specific regions of the brain, where they stop to act as implants without the need for open-skull surgery. Once positioned, they allow for wireless electrical stimulation to treat neurological disorders, eliminating the risks and high costs associated with invasive surgeries. At the end of the video, we can see a microscopic analysis of the Pfizer Covid vaccine conducted in 2022 by Ricardo Delgado, where graphene-based artificial structures are observed that should not be present in the injectable. The images speak for themselves. This technology was implanted without consent and through betrayal in 2022. 📺 Rumble: 📺 Youtube: Please spread this video as well as the attached documents added in the description of this message: ▪️LINK TO VIDEOS AND DOCUMENTS OF GREAT INTEREST: 💯 Video translated into English by the M-Power Translations team. 🌐 Telegram Channel: 🌐 Facebook Channel: ☕️ Support our translations: 💳 Paypal:

🇬🇧🇺🇸 #English - Biodigital Convergence and the Challenge to Free Will: A Critical Analysis by Dr. Geanina Hagima. In this presentation, Dr. Geanina Hagima conducts an exhaustive analysis of what she terms a "global attack on human rights" and the integrity of the human species. The content is broken down into the following fundamental pillars: * Denunciation of Undeclared Components: The doctor refers to findings by independent researchers (citing Lorena Diblasi and Marcela Sangorrín) regarding the presence of up to 55 undeclared elements in recent vaccination technologies. She contends that the use of nanotechnology and artificial intelligence in these products lacked the necessary regulation at the time of their implementation. * Cognitive Warfare and Neurotechnology: She presents the thesis that humanity is in the midst of a "cognitive war" that manipulates the subconscious through technological means. She explains how environmental particles and medical procedures could facilitate nanoparticles crossing the blood-brain barrier via the olfactory nerve, directly affecting neurological functions. * The Transhumanism Agenda: She links the objectives of Agenda 2030 with biodigital convergence, a process that seeks to transform the human being into a "transhuman" entity through the integration of biotechnology and information technology. She criticizes the visions of theorists like Ray Kurzweil, defending the perfection of natural creation against artificial "human enhancement." * Brain-Computer Interfaces (BCI): She warns about recent scientific publications presenting non-invasive interfaces capable of stimulating specific neuronal groups. According to her analysis, although presented as solutions for psychiatric diseases, these tools could be used for the remote control of the human mind. * Call to Action and Legislation: She concludes by emphasizing the urgency of creating legal frameworks that protect free will. She urges the medical community to investigate not only superficial biological effects but also the toxicology of new technologies, exhorting the population to inform themselves to defend the future of coming generations. The attached video shows a "new technology" developed by MIT (Massachusetts Institute of Technology) called "circulatronics," which consists of sub-cellular scale electronic devices that can be injected via a common syringe into the bloodstream. These microchips travel autonomously through the blood vessels until they reach specific regions of the brain, where they stop to act as implants without the need for open-skull surgery. Once positioned, they allow for wireless electrical stimulation to treat neurological disorders, eliminating the risks and high costs associated with invasive surgeries. At the end of the video, we can see a microscopic analysis of the Pfizer Covid vaccine conducted in 2022 by Ricardo Delgado, where graphene-based artificial structures are observed that should not be present in the injectable. The images speak for themselves. This technology was implanted without consent and through betrayal in 2022. 📺 Rumble: 📺 Youtube: Please spread this video as well as the attached documents added in the description of this message: ▪️LINK TO VIDEOS AND DOCUMENTS OF GREAT INTEREST: 💯 Video translated into English by the M-Power Translations team. 🌐 Telegram Channel: 🌐 Facebook Channel: ☕️ Support our translations: 💳 Paypal:

M-Power Translations

27,342 views • 5 months ago

Excited to share TERRA, a tissue world model 🧬 Over ~1.5 years we ran a large data-generation + modelling effort to build a world model for human tissues, pretrained on 112M cells from spatial transcriptomics (mostly Xenium 5000-plex + public data). It's built on one of the largest human spatial transcriptomics corpora assembled to date, spanning 20 tissues across development, health and 26 disease conditions, ~two-thirds newly generated in-house. Why a "world model" for tissue? Images have universal representations (ViT/DINOv3), so do proteins (ESM, Alex Rives) and pathology (UNI, Faisal Mahmood). We've worked hard to build something similar for human tissue: one model that captures its multi-scale logic, genes → cells → their native microenvironments. Like the JEPA approach Yann LeCun has championed, TERRA learns by prediction in embedding space, but for human tissue. How it works: it tokenises each cell together with its nearest neighbours into one sequence while keeping every gene's identity, then masks part of a neighbourhood and predicts the representation of the hidden part, not raw noisy counts. From one backbone it reads out three scales, gene embeddings (what a gene is doing in a cell and its niche), cell embeddings (cell type and state) and neighbourhood embeddings (the niche), and because it keeps gene-level resolution it can knock a gene out in silico and predict the response. Applied entirely zero-shot, TERRA maps and perturbs human tissue across unseen organs, diseases and technologies, outperforming existing spatial approaches. Three take-homes: 1️⃣ One model, any tissue. A single pretrained backbone provides tissue representations zero-shot, handling genes, cells and niches across organs and platforms, off the shelf. 2️⃣ New biology, development to clinic. We built a new spatial atlas of the developing human pancreas and found an islet-associated capillary state that looks like a precursor of mature islet vasculature. In kidney, TERRA's in silico knockouts predicted the tissue-injury programme from cancer immunotherapy (checkpoint blockade), confirmed in treated kidneys, detected in blood, and linked to declining kidney function. 3️⃣ A grammar of tissue architecture. By coupling each cell's state to its niche, TERRA defines recurring cross-organ "archetypes" of macrophage neighbourhoods, including a tumour-boundary niche that tracks poor survival in kidney cancer. TERRA is already in use: it powered our recent skin atlas of hidden immune-memory niches ( with more studies coming soon. This was an amazing collaboration between clinicians, machine-learning scientists and cell biologists 🙏 Led by Sebastian Birk, Vali Sanian Amirhosein Vahidi, Samuel Ogden, Daniyal Jafree, Adib Miraki, Carlo Leonardi and Arpit Merchant, with Lassi Paavolainen, Menna Clatworthy, Omer Ali Bayraktar, Muzlifah Haniffa, Tom Mitchell and Mostafa Bakhti. Huge thanks too to everyone who shared data and helped along the way. What excites me most is seeing how the community builds on this. The model, code and tutorials are all public, so anyone can run TERRA on their own tissues, extend it, or build new models on top. Huge thanks to the whole team across Wellcome Sanger Institute and our many collaborators. 📄 Paper: 💻 Code: 🤗 Model: #SpatialTranscriptomics #SpatialGenomics #FoundationModels #AI4Science #MachineLearning #ComputationalBiology #SingleCell #WorldModels

Excited to share TERRA, a tissue world model 🧬 Over ~1.5 years we ran a large data-generation + modelling effort to build a world model for human tissues, pretrained on 112M cells from spatial transcriptomics (mostly Xenium 5000-plex + public data). It's built on one of the largest human spatial transcriptomics corpora assembled to date, spanning 20 tissues across development, health and 26 disease conditions, ~two-thirds newly generated in-house. Why a "world model" for tissue? Images have universal representations (ViT/DINOv3), so do proteins (ESM, Alex Rives) and pathology (UNI, Faisal Mahmood). We've worked hard to build something similar for human tissue: one model that captures its multi-scale logic, genes → cells → their native microenvironments. Like the JEPA approach Yann LeCun has championed, TERRA learns by prediction in embedding space, but for human tissue. How it works: it tokenises each cell together with its nearest neighbours into one sequence while keeping every gene's identity, then masks part of a neighbourhood and predicts the representation of the hidden part, not raw noisy counts. From one backbone it reads out three scales, gene embeddings (what a gene is doing in a cell and its niche), cell embeddings (cell type and state) and neighbourhood embeddings (the niche), and because it keeps gene-level resolution it can knock a gene out in silico and predict the response. Applied entirely zero-shot, TERRA maps and perturbs human tissue across unseen organs, diseases and technologies, outperforming existing spatial approaches. Three take-homes: 1️⃣ One model, any tissue. A single pretrained backbone provides tissue representations zero-shot, handling genes, cells and niches across organs and platforms, off the shelf. 2️⃣ New biology, development to clinic. We built a new spatial atlas of the developing human pancreas and found an islet-associated capillary state that looks like a precursor of mature islet vasculature. In kidney, TERRA's in silico knockouts predicted the tissue-injury programme from cancer immunotherapy (checkpoint blockade), confirmed in treated kidneys, detected in blood, and linked to declining kidney function. 3️⃣ A grammar of tissue architecture. By coupling each cell's state to its niche, TERRA defines recurring cross-organ "archetypes" of macrophage neighbourhoods, including a tumour-boundary niche that tracks poor survival in kidney cancer. TERRA is already in use: it powered our recent skin atlas of hidden immune-memory niches ( with more studies coming soon. This was an amazing collaboration between clinicians, machine-learning scientists and cell biologists 🙏 Led by Sebastian Birk, Vali Sanian Amirhosein Vahidi, Samuel Ogden, Daniyal Jafree, Adib Miraki, Carlo Leonardi and Arpit Merchant, with Lassi Paavolainen, Menna Clatworthy, Omer Ali Bayraktar, Muzlifah Haniffa, Tom Mitchell and Mostafa Bakhti. Huge thanks too to everyone who shared data and helped along the way. What excites me most is seeing how the community builds on this. The model, code and tutorials are all public, so anyone can run TERRA on their own tissues, extend it, or build new models on top. Huge thanks to the whole team across Wellcome Sanger Institute and our many collaborators. 📄 Paper: 💻 Code: 🤗 Model: #SpatialTranscriptomics #SpatialGenomics #FoundationModels #AI4Science #MachineLearning #ComputationalBiology #SingleCell #WorldModels

Mo Lotfollahi

51,074 views • 1 month ago

I've had many engineers ask me why its worth their time and effort to learn biology in response to this post. Why should they be excited? We are poised for a revolution in biotech that will be uniquely enabled by computers. Convince yourself by digging into the examples I link: - The tooling is getting better. Assays are able to measure a broad array of molecules at a falling cost and increasing throughput. Look to ScaleBio, Curio Bioscience, AtlasXOmics for inspiration. We are sequencing millions of single cells and building spatial maps of the molecular state of tumors. After two generations of "next-generation sequencing", and stagnating DNA read + write costs under the monopoly of Illumina, this wave of the new assays will have a profound impact on the iteration speed and scale of experimentation. Little needs to be said about the impact of compounding trends in core tooling over a sufficient period of time. - Biotechs are using data to guide decisions and are incorporating domain informed machine learning as a core part of the molecular design process. There is great synergy here with better tooling as a means of abundant, cheap data. Look to Recursion, Manifold Bio, Dyno Tx, Asimov. There is also the cross pollination of biology informed architectures with the recent explosion in new machine learning techniques. These models are starting to do useful things, like generate functional gene editing proteins and entire prokaryotic organisms. Look to ESM, AlphaFold3, RFdiffusion. - New classes of therapies - genetic medicines and engineered immune cells - are having real success in the clinic. One dose cures for cardiovascular disease (Verve w ACSD), vaccines for cancer (Moderna w mRNA 4157), in vivo gene editing proteins (CRISPR Tx, Beam, Ensoma), metabolic disease (Novartis, Eli Lily w GLP-1/GIP modulators) are being dosed in real people right now + transforming lives. - The AI craze is commoditizing accelerated hardware and fast storage devices like NVMes, improving developer frameworks for writing code against these devices and maturing the systems tooling for moving around lots of data between computers for distributed training. One happy accident of this bubble will be the reuse of these components to build a new systems stack for the large scale processing of molecular data. This will be very important to construct a 1 billion single cell atlas and beyond. (For reference, the state of the art is ScaleBio's 2M cell kit, dubbed QuantumScale, and it is pushing things with the hardware + software we have today.) - Language models might be the perfect tool to distill the unstructured corpus of public data, literature, and methods sitting around on the Internet into real biological insights for scientist asking questions in natural language. It will also allow them to install, configure and run the slew of useful but poorly maintained academic computational tools to explore and hypothesize new biology on their own. Increasing the productivity of each scientist will do much to reverse Eroom's law. - There is an appetite from the market for new applications of biotech beyond drug development. Bacteria driven lithium mining (maverick), cell agriculture (growing cows in vats), early signs of consumer biologics (Geltor), biofoundries (Ginkgo). My guess is some of the greatest minds of our generation will want to do more than perturb the human body with therapies. I think it is also important to recognize that the need for computers and software is a secular trend in the progression of biotech independent of the interests of Silicon Valley. Clusters of computers, the information they store and the software that runs on them are precisely the technology needed by this field as it transforms into a discipline of information management, towards reducing living things into well characterized building blocks we can rebuild in our image. Software companies, as some local and hyper efficient structure in the arc of capitalism, with established methods and well trod rails to attract resources, talent and easily distribute product to an entire market, are the perfect place to incubate and disseminate these tools. There will probably be many, very large computer companies in biology in the next century.

I've had many engineers ask me why its worth their time and effort to learn biology in response to this post. Why should they be excited? We are poised for a revolution in biotech that will be uniquely enabled by computers. Convince yourself by digging into the examples I link: - The tooling is getting better. Assays are able to measure a broad array of molecules at a falling cost and increasing throughput. Look to ScaleBio, Curio Bioscience, AtlasXOmics for inspiration. We are sequencing millions of single cells and building spatial maps of the molecular state of tumors. After two generations of "next-generation sequencing", and stagnating DNA read + write costs under the monopoly of Illumina, this wave of the new assays will have a profound impact on the iteration speed and scale of experimentation. Little needs to be said about the impact of compounding trends in core tooling over a sufficient period of time. - Biotechs are using data to guide decisions and are incorporating domain informed machine learning as a core part of the molecular design process. There is great synergy here with better tooling as a means of abundant, cheap data. Look to Recursion, Manifold Bio, Dyno Tx, Asimov. There is also the cross pollination of biology informed architectures with the recent explosion in new machine learning techniques. These models are starting to do useful things, like generate functional gene editing proteins and entire prokaryotic organisms. Look to ESM, AlphaFold3, RFdiffusion. - New classes of therapies - genetic medicines and engineered immune cells - are having real success in the clinic. One dose cures for cardiovascular disease (Verve w ACSD), vaccines for cancer (Moderna w mRNA 4157), in vivo gene editing proteins (CRISPR Tx, Beam, Ensoma), metabolic disease (Novartis, Eli Lily w GLP-1/GIP modulators) are being dosed in real people right now + transforming lives. - The AI craze is commoditizing accelerated hardware and fast storage devices like NVMes, improving developer frameworks for writing code against these devices and maturing the systems tooling for moving around lots of data between computers for distributed training. One happy accident of this bubble will be the reuse of these components to build a new systems stack for the large scale processing of molecular data. This will be very important to construct a 1 billion single cell atlas and beyond. (For reference, the state of the art is ScaleBio's 2M cell kit, dubbed QuantumScale, and it is pushing things with the hardware + software we have today.) - Language models might be the perfect tool to distill the unstructured corpus of public data, literature, and methods sitting around on the Internet into real biological insights for scientist asking questions in natural language. It will also allow them to install, configure and run the slew of useful but poorly maintained academic computational tools to explore and hypothesize new biology on their own. Increasing the productivity of each scientist will do much to reverse Eroom's law. - There is an appetite from the market for new applications of biotech beyond drug development. Bacteria driven lithium mining (maverick), cell agriculture (growing cows in vats), early signs of consumer biologics (Geltor), biofoundries (Ginkgo). My guess is some of the greatest minds of our generation will want to do more than perturb the human body with therapies. I think it is also important to recognize that the need for computers and software is a secular trend in the progression of biotech independent of the interests of Silicon Valley. Clusters of computers, the information they store and the software that runs on them are precisely the technology needed by this field as it transforms into a discipline of information management, towards reducing living things into well characterized building blocks we can rebuild in our image. Software companies, as some local and hyper efficient structure in the arc of capitalism, with established methods and well trod rails to attract resources, talent and easily distribute product to an entire market, are the perfect place to incubate and disseminate these tools. There will probably be many, very large computer companies in biology in the next century.

Kenny Workman

113,534 views • 1 year ago

Powerful testimony by Del Bigtree "I just wanna state the obvious, which is just this past week, news headlines described a massive study of ninety nine million people who received the COVID vaccine. The Daily Mail headline says it all. Largest COVID vaccine study ever finds shots are linked to small, increased risk of neurological blood and heart disorders." "And it adds on to the title, but they are still extremely rare. Every article about the study went out of its way, described injuries as rare. But what does rare actually mean? First slide. This is the graph that was in the Daily Mail's article. In terms of this study, what they're saying is rare includes a 3.78 times risk of swelling in the brain and spinal cord." "This means you are increasing your risk of brain and spinal swelling by 378% over someone who didn't get the vaccine. There was also a 2.86 times risk of Guillain Barre syndrome, which is a paralysis, 6.10 times risk of myocarditis, and a 6.91 x risk of pericarditis, swelling of the heart issues. The question no one in the media seems to be asking, I think, is if each of these potential injuries is rare, is it still rare when you add them all together?" "Take the Moderna vaccine, for example. In the standard three shot regimen, based on this study, a person is increasing their risk of brain and spinal swelling by 378% with the first shot. They're also adding a 348% risk of myocarditis with that same first shot, a 610% increase of myocarditis with the second shot, and another 201% increased risk of myocarditis with the third shot." "And these are just the adverse events that were the focus of the study. We're talking about cancer and all sorts of other things that we should be looking at. When the CDC was creating the v safe app, app to track the health outcomes of the first ten million people who received the COVID vaccine, they had a list of adverse events of special interest." "These were injuries that the CDC had reason to believe could be caused by the COVID vaccine. That list includes acute myocardial infarction, anaphylaxis, coagulopathy, death, Guillain Barre syndrome, Kawasaki disease, multisystem inflammatory disease, narcolepsy, seizures, convulsions, stroke, and transverse myelitis. Now let's just assume that all these issues are rare." "And since we know that the rare is currently being being described, at least in this study, as anything between a two hundred percent increase to a nearly seven hundred percent increased risk, then what is the actual risk when you add all these potential adverse outcomes together? Further still, how high is the risk when you multiply all of these risks by five doses of the COVID vaccine?" "Are we still in the ballpark of rare? Now imagine multiplying all of these known risks by 72 doses. Now you've just considered the amount of risk that every child is facing with the CDC recommended schedule. The CDC childhood schedule has been the focus of my nonprofit, ICANS, work since the February when it was founded. Through FOIA requests and lawsuits against our regulatory agencies, we've uncovered many inconvenient truths." "Perhaps the most significant finding is that none of the 14 routine vaccines on the CDC recommended schedule, which are delivered in approximately 72, was ever put through a long term, double blind, placebo based safety trial prior to licensure. Since this type of trial is really the only way to establish that a pharmaceutical product is safe, it is misinformation to state that the vaccines are safe." "We have skipped the study that would allow you to make that statement scientifically. Most people don't realize that there's a list of known side effects on the information sheet provided with every vaccine that is shipped. Here is just a partial list of printed adverse events for just one of the hepatitis b vaccines, Engerix b." "Here are the side effects. Herp b zoster, meningitis, thrombocytopenia, anaphylaxis, hypersensitivity syndrome, arthralgia, arthritis, urticaria, erythema multiforme, encephalopathy, swelling of the brain just like the COVID vaccine, multiple sclerosis, neuritis, hypoesthesia, paresthesia, Guillain Barre syndrome, paralysis, Bell's palsy, optic neuritis, paralysis, paresis, seizures, syncope, transverse myelitis, conjunctivitis, keratitis, tinnitus, vertigo, tachycardia, apnea, bronchospasms, including asthma like symptoms, dyspepsia, alopecia, angioedema, eczema, and Stevens Johnson Syndrome. That's just one vaccine." "That vaccine manufacturer has all these side effects in the warning list because why? It is stipulated by the FDA that there is a reasonable belief that they are causally related to the vaccine. That's why they're there. They're not adding them just because they think they should, because they have to. The warning label lists nearly 50 potential side effects, many of them serious, and that is just the first vaccine given to a baby on their first day of life. By the way, the safety study for that hepatitis b vaccine was only four days long and had no placebo comparator. That is not science." "That's insanity. We currently have a lawsuit trying to have that vaccine removed until they do proper safety testing. Every one of the childhood vaccines has a similar list of side effects. And though they are considered rare, how rare is it when you multiply roughly 50 potential side effects 72 times, which is the total number of doses given to a child by the time they're 18? The revelations from the recent study of the COVID vaccine explains what we've been saying for years." "Vaccines are not completely safe. And those side effects are rare. What happens when you add them all together? Perhaps it looks like this. Last slide. This is what Brian Hooker is talking about. In the nineteen eighties, when we were giving 11 of about three vaccines, the chronic illness rate, which includes neurological and autoimmune disease, was twelve point eight percent." "Once we passed the 1986 act and we had the gold rush of vaccines, it exploded to 53. As I said, seventy two that's fifty three shots, seventy two doses. You watch the chronic illness rate, neurological and autoimmune disease skyrocket to fifty four percent of our children. And by the way, that study was finished up in 2011, 2012. We had have no idea since then how bad this has gotten." "But what you were looking right at there is the greatest decline in public health in human history. Never have we watched that many children in just a few decades have their immune systems start fighting their own bodies and swelling brains. And when you look at the numbers that Brian Hooker just showed you, they match exactly what we're seeing them call rare in this COVID study." "Five times rate of neurological disorders. Vaxxed versus unvaxxed showing about four times rate of autism in people that got the vaccine compared to those that don't. So it's rare, but it's possible, and it's real. And when we look at those rare numbers stacked up, especially with autism, we're now at one in forty five. That's conservative. Many say one in thirty five children is being diagnosed with autism. Roughly one in twenty to twenty four boys. Is that still rare? Sure. Sure." "It's just a couple per one hundred. But what we can never say again after this study and what we all now know is that vaccine injury isn't happening. That's a lie. It is. And we all have a threshold, and we should figure out what that threshold is because millions of children are being injured all around the world. Nothing to see here. Right? Nothing to see here."

Powerful testimony by Del Bigtree "I just wanna state the obvious, which is just this past week, news headlines described a massive study of ninety nine million people who received the COVID vaccine. The Daily Mail headline says it all. Largest COVID vaccine study ever finds shots are linked to small, increased risk of neurological blood and heart disorders." "And it adds on to the title, but they are still extremely rare. Every article about the study went out of its way, described injuries as rare. But what does rare actually mean? First slide. This is the graph that was in the Daily Mail's article. In terms of this study, what they're saying is rare includes a 3.78 times risk of swelling in the brain and spinal cord." "This means you are increasing your risk of brain and spinal swelling by 378% over someone who didn't get the vaccine. There was also a 2.86 times risk of Guillain Barre syndrome, which is a paralysis, 6.10 times risk of myocarditis, and a 6.91 x risk of pericarditis, swelling of the heart issues. The question no one in the media seems to be asking, I think, is if each of these potential injuries is rare, is it still rare when you add them all together?" "Take the Moderna vaccine, for example. In the standard three shot regimen, based on this study, a person is increasing their risk of brain and spinal swelling by 378% with the first shot. They're also adding a 348% risk of myocarditis with that same first shot, a 610% increase of myocarditis with the second shot, and another 201% increased risk of myocarditis with the third shot." "And these are just the adverse events that were the focus of the study. We're talking about cancer and all sorts of other things that we should be looking at. When the CDC was creating the v safe app, app to track the health outcomes of the first ten million people who received the COVID vaccine, they had a list of adverse events of special interest." "These were injuries that the CDC had reason to believe could be caused by the COVID vaccine. That list includes acute myocardial infarction, anaphylaxis, coagulopathy, death, Guillain Barre syndrome, Kawasaki disease, multisystem inflammatory disease, narcolepsy, seizures, convulsions, stroke, and transverse myelitis. Now let's just assume that all these issues are rare." "And since we know that the rare is currently being being described, at least in this study, as anything between a two hundred percent increase to a nearly seven hundred percent increased risk, then what is the actual risk when you add all these potential adverse outcomes together? Further still, how high is the risk when you multiply all of these risks by five doses of the COVID vaccine?" "Are we still in the ballpark of rare? Now imagine multiplying all of these known risks by 72 doses. Now you've just considered the amount of risk that every child is facing with the CDC recommended schedule. The CDC childhood schedule has been the focus of my nonprofit, ICANS, work since the February when it was founded. Through FOIA requests and lawsuits against our regulatory agencies, we've uncovered many inconvenient truths." "Perhaps the most significant finding is that none of the 14 routine vaccines on the CDC recommended schedule, which are delivered in approximately 72, was ever put through a long term, double blind, placebo based safety trial prior to licensure. Since this type of trial is really the only way to establish that a pharmaceutical product is safe, it is misinformation to state that the vaccines are safe." "We have skipped the study that would allow you to make that statement scientifically. Most people don't realize that there's a list of known side effects on the information sheet provided with every vaccine that is shipped. Here is just a partial list of printed adverse events for just one of the hepatitis b vaccines, Engerix b." "Here are the side effects. Herp b zoster, meningitis, thrombocytopenia, anaphylaxis, hypersensitivity syndrome, arthralgia, arthritis, urticaria, erythema multiforme, encephalopathy, swelling of the brain just like the COVID vaccine, multiple sclerosis, neuritis, hypoesthesia, paresthesia, Guillain Barre syndrome, paralysis, Bell's palsy, optic neuritis, paralysis, paresis, seizures, syncope, transverse myelitis, conjunctivitis, keratitis, tinnitus, vertigo, tachycardia, apnea, bronchospasms, including asthma like symptoms, dyspepsia, alopecia, angioedema, eczema, and Stevens Johnson Syndrome. That's just one vaccine." "That vaccine manufacturer has all these side effects in the warning list because why? It is stipulated by the FDA that there is a reasonable belief that they are causally related to the vaccine. That's why they're there. They're not adding them just because they think they should, because they have to. The warning label lists nearly 50 potential side effects, many of them serious, and that is just the first vaccine given to a baby on their first day of life. By the way, the safety study for that hepatitis b vaccine was only four days long and had no placebo comparator. That is not science." "That's insanity. We currently have a lawsuit trying to have that vaccine removed until they do proper safety testing. Every one of the childhood vaccines has a similar list of side effects. And though they are considered rare, how rare is it when you multiply roughly 50 potential side effects 72 times, which is the total number of doses given to a child by the time they're 18? The revelations from the recent study of the COVID vaccine explains what we've been saying for years." "Vaccines are not completely safe. And those side effects are rare. What happens when you add them all together? Perhaps it looks like this. Last slide. This is what Brian Hooker is talking about. In the nineteen eighties, when we were giving 11 of about three vaccines, the chronic illness rate, which includes neurological and autoimmune disease, was twelve point eight percent." "Once we passed the 1986 act and we had the gold rush of vaccines, it exploded to 53. As I said, seventy two that's fifty three shots, seventy two doses. You watch the chronic illness rate, neurological and autoimmune disease skyrocket to fifty four percent of our children. And by the way, that study was finished up in 2011, 2012. We had have no idea since then how bad this has gotten." "But what you were looking right at there is the greatest decline in public health in human history. Never have we watched that many children in just a few decades have their immune systems start fighting their own bodies and swelling brains. And when you look at the numbers that Brian Hooker just showed you, they match exactly what we're seeing them call rare in this COVID study." "Five times rate of neurological disorders. Vaxxed versus unvaxxed showing about four times rate of autism in people that got the vaccine compared to those that don't. So it's rare, but it's possible, and it's real. And when we look at those rare numbers stacked up, especially with autism, we're now at one in forty five. That's conservative. Many say one in thirty five children is being diagnosed with autism. Roughly one in twenty to twenty four boys. Is that still rare? Sure. Sure." "It's just a couple per one hundred. But what we can never say again after this study and what we all now know is that vaccine injury isn't happening. That's a lie. It is. And we all have a threshold, and we should figure out what that threshold is because millions of children are being injured all around the world. Nothing to see here. Right? Nothing to see here."

Camus

46,394 views • 1 year ago

Scientists discover surprising link between gut-brain interactions and mental health | Eric W. Dolan, PsyPost A new study provides evidence that the connection between the brain and the stomach may be linked to mental health in a measurable way. Researchers from Aarhus University in Denmark, publishing their work in Nature Mental Health, report that a specific pattern of communication between the brain and the stomach reflects how individuals feel emotionally and psychologically. Their findings suggest that these gut-brain interactions can indicate a person’s levels of anxiety, depression, well-being, and overall quality of life. The idea that emotions are linked to physical sensations in the gut is widely reflected in language. People often talk about having “butterflies in the stomach” when nervous, or feeling “sick to the stomach” when distressed. Yet, despite these common expressions, most scientific attention in the field of brain-body interaction has focused on other organs, such as the heart and lungs. These areas have long been studied for their roles in emotion and mood. The researchers were struck by how little was known about how the stomach, in particular, interacts with the brain. While recent studies have explored the influence of gut bacteria and digestion on mental health, very little work had been done on the electrical rhythms of the stomach and how they may directly communicate with the brain’s networks involved in emotion, attention, and cognition. The team behind this new study wanted to explore whether a person’s psychological profile might be reflected in how strongly the stomach and brain are coupled during rest. Their aim was not to link a specific diagnosis like depression to a single brain region, but rather to identify patterns across a broad spectrum of mental health experiences. “Our interest grew from the long-standing discussion about the role of the body in shaping emotion, a question that has fascinated philosophers and scientists for centuries,” said study author Leah Banellis (Leah Banellis), a postdoctoral fellow in Cognitive Neuroscience at Aarhus University. “Yet, while the heart and lungs have received much attention, the stomach has been largely overlooked. This gap struck us as especially surprising, because the link between the stomach and emotional experience feels so intuitive. It is heavily reflected in everyday language, with phrases like ‘butterflies in the stomach,’ ‘sick to our stomach,’ or ‘trust your gut.'” The research was part of the Visceral Mind Project, a large-scale initiative that combines data on brain activity, bodily rhythms, and psychological assessments. The team recorded data from 243 people using a method that captures both electrical signals from the stomach (electrogastrography) and brain activity measured with functional magnetic resonance imaging (fMRI). The participants represented a wide range of mental health profiles, from those reporting high well-being to others showing signs of distress, including anxiety, depression, fatigue, and insomnia. To capture this diversity, the researchers didn’t exclude people with psychiatric symptoms or diagnoses. Instead, they aimed for variation, which would allow their models to detect patterns across the mental health spectrum. Each participant underwent a series of recordings while lying still in the MRI scanner. At the same time, sensors on the abdomen captured the stomach’s slow electrical rhythm, which cycles about three times per minute. This rhythm, which originates from specialized cells in the stomach lining, is typically involved in coordinating digestion. But the researchers suspected it might also be linked to mental state. To analyze the relationship between stomach and brain activity, the team used a method that looks at how well the two rhythms align over time. This measure, known as phase-locking value, essentially captures the degree of synchronization between stomach signals and brain signals across different regions. The researchers then combined this data with results from a comprehensive mental health questionnaire. The battery included 37 different scores across a range of domains—such as anxiety, stress, mood, fatigue, attention, sleep quality, and life satisfaction. Using a statistical method known as canonical correlation analysis, they looked for patterns that linked brain-stomach coupling with the participants’ mental health profiles. The analysis revealed a clear and statistically significant pattern. Stronger coupling between the stomach’s rhythm and brain activity was associated with poorer mental health. Individuals who reported more symptoms of anxiety, depression, stress, and fatigue tended to show increased synchronization between their stomach and brain rhythms. In contrast, those with higher levels of well-being and life satisfaction showed weaker coupling. “For the first time, we’ve found a scientific link between your ‘gut feelings’ and your mental health, showing a surprising connection between your stomach’s natural rhythm and your brain,” Banellis told PsyPost. “Specifically, our study revealed that stronger communication between the stomach and brain is linked to worse mental health, such as higher symptoms of anxiety, depression, stress, and fatigue, whereas weaker stomach-brain communication aligns with better mental health reflected in higher overall well-being and quality of life.” This stomach-brain signature was not random. It was localized in specific brain networks, particularly those involved in attention, cognitive control, and salience detection. Some of the strongest associations were found in regions like the superior angular gyrus and the posterior frontal and parietal areas—regions often implicated in cognitive tasks and mental health disorders. Importantly, the researchers ran multiple control analyses to ensure the robustness of their findings. They ruled out the possibility that the observed effects were simply due to general brain activity patterns, fluctuations in heart rate or breathing, or basic features of stomach physiology. In other words, the association appeared specific to the coupling between the stomach’s electrical rhythm and particular brain networks—not just a general marker of body or brain state. Their approach was designed to detect broad psychological dimensions rather than focus on one diagnosis. The strongest psychological pattern they found was a spectrum ranging from negative affective states (like anxiety and depression) to positive traits (like well-being and quality of life). This result suggests that the stomach-brain connection is not tied to any one disorder but instead reflects a general mode of psychological functioning. “Anxiety, depression, stress, and fatigue showed the strongest links to stomach-brain communication,” Banellis explained. “While phrases like ‘butterflies in the stomach’ or feeling ‘sick to your stomach’ are common ways we describe emotional distress, it was surprising to find such consistent and clear evidence across these symptoms. Even more unexpected was the direction of the effect: we might have assumed that stronger alignment between the body and brain would be beneficial. Instead, our findings suggest that heightened stomach-brain communication could act more like a warning signal, an internal alarm system reflecting mental strain rather than harmony.” Read more:

Owen Gregorian

92,301 views • 11 months ago

War Diary Day 1,391 Blaise Metreweli, the Chief of Britain's Secret Intelligence Service, sticks it to the Killer in The Kremlin. And all his creepy helpers. I agree with every fucking word. VPDFO! (Transcript of the speech, exactly as it was delivered) 📷 Welcome inside MI6. This iconic building, familiar to movie fans everywhere, is the home of Britain’s foreign intelligence agency. But whilst hundreds of my team pass through the entry pods each day, the truth is that most of our work happens many miles away from this place - out of sight, hidden from the world, undercover, recruiting and running agents who choose to place their trust in us, sharing secrets to make the UK and the world safer. You might pass one of our officers on the street or sit next to them on a plane when you’re about to set off on an adventure of your own, or in a foreign city taking selfies by the sights. Whether it’s in seemingly everyday places, or on the front line embedded with our military, MI6 is there. In my first few weeks, I’ve heard repeatedly that MI6 is trusted and respected globally, two things that we never take for granted. We are seen as a source of hard power, soft influence and rapid innovation. I’ve also heard that people want to believe in MI6. It’s my job to make sure they can. Today, I want to talk about human agency. We all have choices to make about how we deal with the undercurrents shaping our world. About how, in our new, faster, more dangerous and technology-mediated world, it will be our rediscovery of our shared humanity, our ability to listen, and our courage that will determine how our future unfolds. Conflict is not inevitable. Understanding human nature is in my bones. From a family shaped by devastating conflict, I grew up with a deep sense of gratitude for the UK’s precious democracy and freedom. I spent much of my childhood overseas, which is where my passion for travel and adventure began. I studied anthropology, and later psychology and AI, exploring how we make sense of the world and each other. It’s why I was drawn to MI6: it offers strong purpose, a chance to serve and a belief in the positive power of human connection. Like the Service, I’m operational to my very core. Over nearly three decades, my career has involved recruiting and running agents in hostile territory; and leading operations in warzones to defuse threats and support peace. Always in teams, always learning from others. Over the years, I’ve worked with hundreds of brilliant partners – and indeed occasionally those we’d label as adversaries – across dozens of countries, tackling weapons proliferation and terrorism. During my time at MI5, I saw close up what it takes to defend Britain from being targeted by hostile states. You’ll find many like me in my organisation: powerfully motivated to protect our precious country; curious about how our world is changing, joining dots and taking action, across domains. But it was in my last role as ‘Q’, where it was my job to turn emerging technologies from threats to opportunities that I could most see the world changing. As I dug deep into data and extraordinary innovation, I could see how technology was rapidly reshaping not just our capabilities but also conflict and trust, truth and global power. Let me lay out how I see the global issues MI6 must tackle. Because the greatest danger we face is to misunderstand the nature of the problem. Let’s be in no doubt. Our world is more dangerous and contested now than it has been for decades. Conflict is evolving and trust eroding, just as new technologies spur both competition and dependence. We are being contested from sea to space, from the battlefield to the boardroom. And even our brains, as disinformation manipulates our understanding of each other and ourselves. Across the globe, we are now confronting not one single danger, but an interlocking web of security challenges – military, technological, social, ethical even – each shaping the other in complex ways. We are now operating in a space between peace and war. This is not a temporary state or a gradual, inevitable evolution. Our world is being actively remade, with profound implications for national and international security. Institutions which were designed in the ashes of the Second World War are being challenged. New blocs and identities forming and alliances reshaping. Multipolar competition in tension with multilateral cooperation. But there’s something distinctive that will make this change unlike any other: the impact of advanced technologies, which will accelerate the pace and scale of every threat and opportunity, and increasingly, individualise them too. Advances in artificial intelligence, biotechnology, and quantum computing are not only revolutionising economies but rewriting the reality of conflict, as they ‘converge’ to create science-fiction-like tools. There’s incredible promise in all this for all of us, from green technologies to hyper-personalised medicine. But also peril. AI-powered robots and drones are brilliant for scaled manufacturing but devastating on the battlefield. Discoveries that cure disease can also create new weapons. And as states race for tech supremacy, or as some algorithms become as powerful as states, those hyper-personalised tools could become a new vector for conflict and control. Power itself is becoming more diffuse, more unpredictable as control over these technologies is shifting from states to corporations, and sometimes to individuals. And at the same time, the foundations of trust in our societies are eroding. Information, once a unifying force, is increasingly weaponised. Falsehood spreads faster than fact, dividing communities and distorting reality. We live in an age of hyper-connection yet profound isolation. The algorithms flatter our biases and fracture our public squares. And as trust collapses, so does our shared sense of truth – one of the greatest losses a society can suffer. The defining challenge of the twenty-first century is not simply who wields the most powerful technologies, but who guides them with the greatest wisdom. Our security, our prosperity, and our humanity depend on it. Our world is being remade. And for the first time, we are all at the heart of it. My Service must now operate in this new context too: not just expert on hostile states, terrorism, proliferation and more, but also fluent in technology, able to anticipate the second and third order effects of advances that reshape the world in minutes not months. And as China will be a central part of the global transformation taking place this century, it is essential that we, as MI6, continue to inform the government’s understanding of China’s rise and the implications for UK national security. I’m going to break with tradition and won’t give you a global threat tour, but will focus here on Putin’s Russia. We all continue to face the menace of an aggressive, expansionist and revisionist Russia, seeking to subjugate Ukraine and harass NATO. I find it harrowing that hundreds of thousands have died, with the toll mounting every day, because of Putin’s historical distortions and his compromised desire for respect. He is dragging out negotiations and shifting the cost of war onto his own population. But Putin should be in no doubt, our support is enduring. The pressure we apply on Ukraine’s behalf will be sustained. Because it is fundamental not just to European sovereignty and security but to global stability. Alongside the grinding war, Russia is testing us in the grey zone with tactics that are just below the threshold of war. It’s important to understand their attempts to bully, fearmonger and manipulate, because it affects us all. I am talking about: Cyberattacks on critical infrastructure. Drones buzzing airports and bases. Aggressive activity in our seas, above and below the waves. State-sponsored arson and sabotage. Propaganda and influence operations that crack open and exploit fractures within societies. Countering this activity is the work of intelligence and security services across Europe and the globe. And as the Foreign Secretary made clear in a speech last week, the UK is defending itself against this Russian information warfare – sanctioning Russian media outlets pushing Kremlin narratives. The export of chaos is a feature not a bug in this Russian approach to international engagement; and we should be ready for this to continue until Putin is forced to change his calculus. So, how should we respond? It’s not enough now just to understand the world. We must shape it too. MI6 is well-positioned to respond to these threats and wider global instability. And we will continue to evolve, just as we have throughout our long history. The UK government has invested in our intelligence agencies and we are all using our unique powers to keep the British people safe. Our ‘open and connected’ partnerships across the UK Intelligence Community, with HMGCC, NSSIF and the wider tech ecosystem in the UK will become even more important – because in the digital battleground, no single organisation can prevail alone. As a global agency, MI6’s inbuilt strength is our partners and our people. The risks I have set out require us to work ever more closely with our colleagues in MI5, GCHQ and in defence and diplomacy. But also with our Five Eyes partners, with the E3, the EU, NATO, those across the Middle East, the Indo-Pacific and beyond. And with many valued partners whose identity needs to remain secret. Together, we integrate our diverse talent, data and tools to meet the threat. AI is a domain in which we will excel, using the technology to augment, not replace, our human skills. Every digital trace, every byte of data, every algorithmic decision has implications for the safety of the lives of the courageous people who work with us as officers and agents, and for the UK’s strategic advantage. Mastery of technology will infuse everything we do. Not just in our labs, but in the field, in our tradecraft, and even more importantly, in the mindset of every officer. We will become as comfortable with lines of code as we are with human sources, as fluent in Python as we are in multiple other languages. Under my leadership, MI6 will continue to attract Britain’s best and most creative minds: linguists and data scientists, case officers and engineers, behavioural experts and technologists. We need people who walk in the shoes and get in the heads of our adversaries. We need people who think differently, challenge assumptions, and act decisively. All can thrive and make a difference at MI6. At an operational level, we will sharpen our edge and impact with audacity, tapping into – if you like – our historical SOE instincts. We’re at our best when we’re hustling to make things happen, because our intelligence is most valuable when it changes reality on the ground. We will take calculated risks, where the prize is significant and the national interest clear. We will never stoop to the tactics of our opponents. But we must seek to outplay them. In every domain. In every way. So intelligence must drive action. Action must deliver advantage. And advantage must serve Britain’s security and prosperity. But at the core, our deeper contribution is also our simplest – how we unlock human agency. Our fast-paced, tech and threat-infused world now generates more heat than light. As nations retrench and rearm, we are losing opportunities to listen to what’s really going on. I’ve seen time and again throughout my career, that this is where MI6 matters most: we listen and we hear. We understand, because we take time to learn languages and cultures, complex technical and historical detail, immerse ourselves in what’s really driving the situation. Across the globe, right now, our officers are finding people with the courage to step forward, and they are taking time to sit and listen to break these tightening cycles of violence. They listen for nuance, for connection, for opportunity. Over the years, I’ve listened to terrorists who have told us how to defuse the bomb because they know that more violence won’t help. To proliferators and smugglers who’ve told us where to find the dangerous material, motivated to protect their children’s future. To people trapped in authoritarian regimes who know, deep down, that their humanity is being chipped away – and that telling us what’s really going on is an important release, allowing us all to find better ways to navigate our changing world. So, we will work with our agents. And we will continue to engage directly, and with respect, with states and organisation currently working against us. Away from the glare of the media, we will use MI6’s convening power wherever we can to make a material difference, bringing parties together to defuse tensions. But the response to the increasing risks we face won’t be delivered by the UK intelligence community alone. Wider society has a role to play too. That includes work taking place in schools across the country so our children don’t get duped by information manipulation. Let’s all check sources, consider evidence, and be alive to those algorithms that trigger intense reactions, like fear. It also means everyone in society really understanding the world we are in – a world where terrorists plot against us, where our enemies fearmonger, bully and manipulate, and the front line is everywhere. Online, on our streets, in our supply chains, in the minds and on the screens of our citizens. We must all stand together against this. As we do today with our friends in Australia after the shocking antisemitic terrorist attack this weekend. My thoughts -and those of my whole organisation – are with the family, friends and loved ones of the victims. Light will always win over darkness. In rising to meet these challenges we, in MI6, will remain anchored to our values: courage, creativity, respect and integrity. And to our principles: accountability and trust are not constraints on our work; they are the foundations of our legitimacy with the British public. Recently, I had the privilege of meeting and thanking a foreign agent who has worked with us for decades, taking extraordinary risks to help keep the UK safe. I asked why. They said simply, ‘Your values. Your integrity and respect. None of us have a future without them’. This moment reinforced to me that we must remain a very human agency. And so, to sustain that trust, MI6 will continue to be more open. Not for the sake of visibility, but because it matters – and as my MI5 counterpart Sir Ken McCallum said recently - because it is a strength. We will continue the practice of speaking publicly, broaden our channels of engagement, and sustain our focus on attracting the most diverse talent to join our Service. Transparency does not mean revealing what must remain secret. It means showing the British people who we are, what we stand for, and why our work matters. We need your trust and support for the difficult and often dangerous work our agents pursue, every day of the year. In an age of uncertainty, one constant remains: the choices made by human beings still determine the shape of the world. Yes, technology can illuminate possibilities: but information requires judgement; complexity demands clarity; and only people can decide which path to follow. The United Kingdom’s global voice has never rested solely on strength – it has rested on trust, principle, and the ability to understand others as well as ourselves. That is also the essence of intelligence: not simply knowing the world, but interpreting it through a uniquely human lens. Ours is the quiet service, the hidden service. It is one rooted in a profound belief that when human beings act with purpose and integrity, they can steady a faltering world. When the Berlin Wall fell, it was our shared belief in freedom that carried Europe forward. When acts of terror targeted open societies, it was intelligence, cooperation and resolve that preserved them. And when adversaries blur fact and falsehood, our task is to defend the space where truth can still stand. As we step into the future, the tools at our disposal will evolve. But what will always matter most is the human element – the person who stands in the shadows and says: this is right, and that is wrong. That choice – the exercise of human agency – has shaped our world before, and it will shape it again. Because in the end, it is not what we can do that defines us, but what we choose to do. Thank you. Published 15 December 2025

War Diary Day 1,391 Blaise Metreweli, the Chief of Britain's Secret Intelligence Service, sticks it to the Killer in The Kremlin. And all his creepy helpers. I agree with every fucking word. VPDFO! (Transcript of the speech, exactly as it was delivered) 📷 Welcome inside MI6. This iconic building, familiar to movie fans everywhere, is the home of Britain’s foreign intelligence agency. But whilst hundreds of my team pass through the entry pods each day, the truth is that most of our work happens many miles away from this place - out of sight, hidden from the world, undercover, recruiting and running agents who choose to place their trust in us, sharing secrets to make the UK and the world safer. You might pass one of our officers on the street or sit next to them on a plane when you’re about to set off on an adventure of your own, or in a foreign city taking selfies by the sights. Whether it’s in seemingly everyday places, or on the front line embedded with our military, MI6 is there. In my first few weeks, I’ve heard repeatedly that MI6 is trusted and respected globally, two things that we never take for granted. We are seen as a source of hard power, soft influence and rapid innovation. I’ve also heard that people want to believe in MI6. It’s my job to make sure they can. Today, I want to talk about human agency. We all have choices to make about how we deal with the undercurrents shaping our world. About how, in our new, faster, more dangerous and technology-mediated world, it will be our rediscovery of our shared humanity, our ability to listen, and our courage that will determine how our future unfolds. Conflict is not inevitable. Understanding human nature is in my bones. From a family shaped by devastating conflict, I grew up with a deep sense of gratitude for the UK’s precious democracy and freedom. I spent much of my childhood overseas, which is where my passion for travel and adventure began. I studied anthropology, and later psychology and AI, exploring how we make sense of the world and each other. It’s why I was drawn to MI6: it offers strong purpose, a chance to serve and a belief in the positive power of human connection. Like the Service, I’m operational to my very core. Over nearly three decades, my career has involved recruiting and running agents in hostile territory; and leading operations in warzones to defuse threats and support peace. Always in teams, always learning from others. Over the years, I’ve worked with hundreds of brilliant partners – and indeed occasionally those we’d label as adversaries – across dozens of countries, tackling weapons proliferation and terrorism. During my time at MI5, I saw close up what it takes to defend Britain from being targeted by hostile states. You’ll find many like me in my organisation: powerfully motivated to protect our precious country; curious about how our world is changing, joining dots and taking action, across domains. But it was in my last role as ‘Q’, where it was my job to turn emerging technologies from threats to opportunities that I could most see the world changing. As I dug deep into data and extraordinary innovation, I could see how technology was rapidly reshaping not just our capabilities but also conflict and trust, truth and global power. Let me lay out how I see the global issues MI6 must tackle. Because the greatest danger we face is to misunderstand the nature of the problem. Let’s be in no doubt. Our world is more dangerous and contested now than it has been for decades. Conflict is evolving and trust eroding, just as new technologies spur both competition and dependence. We are being contested from sea to space, from the battlefield to the boardroom. And even our brains, as disinformation manipulates our understanding of each other and ourselves. Across the globe, we are now confronting not one single danger, but an interlocking web of security challenges – military, technological, social, ethical even – each shaping the other in complex ways. We are now operating in a space between peace and war. This is not a temporary state or a gradual, inevitable evolution. Our world is being actively remade, with profound implications for national and international security. Institutions which were designed in the ashes of the Second World War are being challenged. New blocs and identities forming and alliances reshaping. Multipolar competition in tension with multilateral cooperation. But there’s something distinctive that will make this change unlike any other: the impact of advanced technologies, which will accelerate the pace and scale of every threat and opportunity, and increasingly, individualise them too. Advances in artificial intelligence, biotechnology, and quantum computing are not only revolutionising economies but rewriting the reality of conflict, as they ‘converge’ to create science-fiction-like tools. There’s incredible promise in all this for all of us, from green technologies to hyper-personalised medicine. But also peril. AI-powered robots and drones are brilliant for scaled manufacturing but devastating on the battlefield. Discoveries that cure disease can also create new weapons. And as states race for tech supremacy, or as some algorithms become as powerful as states, those hyper-personalised tools could become a new vector for conflict and control. Power itself is becoming more diffuse, more unpredictable as control over these technologies is shifting from states to corporations, and sometimes to individuals. And at the same time, the foundations of trust in our societies are eroding. Information, once a unifying force, is increasingly weaponised. Falsehood spreads faster than fact, dividing communities and distorting reality. We live in an age of hyper-connection yet profound isolation. The algorithms flatter our biases and fracture our public squares. And as trust collapses, so does our shared sense of truth – one of the greatest losses a society can suffer. The defining challenge of the twenty-first century is not simply who wields the most powerful technologies, but who guides them with the greatest wisdom. Our security, our prosperity, and our humanity depend on it. Our world is being remade. And for the first time, we are all at the heart of it. My Service must now operate in this new context too: not just expert on hostile states, terrorism, proliferation and more, but also fluent in technology, able to anticipate the second and third order effects of advances that reshape the world in minutes not months. And as China will be a central part of the global transformation taking place this century, it is essential that we, as MI6, continue to inform the government’s understanding of China’s rise and the implications for UK national security. I’m going to break with tradition and won’t give you a global threat tour, but will focus here on Putin’s Russia. We all continue to face the menace of an aggressive, expansionist and revisionist Russia, seeking to subjugate Ukraine and harass NATO. I find it harrowing that hundreds of thousands have died, with the toll mounting every day, because of Putin’s historical distortions and his compromised desire for respect. He is dragging out negotiations and shifting the cost of war onto his own population. But Putin should be in no doubt, our support is enduring. The pressure we apply on Ukraine’s behalf will be sustained. Because it is fundamental not just to European sovereignty and security but to global stability. Alongside the grinding war, Russia is testing us in the grey zone with tactics that are just below the threshold of war. It’s important to understand their attempts to bully, fearmonger and manipulate, because it affects us all. I am talking about: Cyberattacks on critical infrastructure. Drones buzzing airports and bases. Aggressive activity in our seas, above and below the waves. State-sponsored arson and sabotage. Propaganda and influence operations that crack open and exploit fractures within societies. Countering this activity is the work of intelligence and security services across Europe and the globe. And as the Foreign Secretary made clear in a speech last week, the UK is defending itself against this Russian information warfare – sanctioning Russian media outlets pushing Kremlin narratives. The export of chaos is a feature not a bug in this Russian approach to international engagement; and we should be ready for this to continue until Putin is forced to change his calculus. So, how should we respond? It’s not enough now just to understand the world. We must shape it too. MI6 is well-positioned to respond to these threats and wider global instability. And we will continue to evolve, just as we have throughout our long history. The UK government has invested in our intelligence agencies and we are all using our unique powers to keep the British people safe. Our ‘open and connected’ partnerships across the UK Intelligence Community, with HMGCC, NSSIF and the wider tech ecosystem in the UK will become even more important – because in the digital battleground, no single organisation can prevail alone. As a global agency, MI6’s inbuilt strength is our partners and our people. The risks I have set out require us to work ever more closely with our colleagues in MI5, GCHQ and in defence and diplomacy. But also with our Five Eyes partners, with the E3, the EU, NATO, those across the Middle East, the Indo-Pacific and beyond. And with many valued partners whose identity needs to remain secret. Together, we integrate our diverse talent, data and tools to meet the threat. AI is a domain in which we will excel, using the technology to augment, not replace, our human skills. Every digital trace, every byte of data, every algorithmic decision has implications for the safety of the lives of the courageous people who work with us as officers and agents, and for the UK’s strategic advantage. Mastery of technology will infuse everything we do. Not just in our labs, but in the field, in our tradecraft, and even more importantly, in the mindset of every officer. We will become as comfortable with lines of code as we are with human sources, as fluent in Python as we are in multiple other languages. Under my leadership, MI6 will continue to attract Britain’s best and most creative minds: linguists and data scientists, case officers and engineers, behavioural experts and technologists. We need people who walk in the shoes and get in the heads of our adversaries. We need people who think differently, challenge assumptions, and act decisively. All can thrive and make a difference at MI6. At an operational level, we will sharpen our edge and impact with audacity, tapping into – if you like – our historical SOE instincts. We’re at our best when we’re hustling to make things happen, because our intelligence is most valuable when it changes reality on the ground. We will take calculated risks, where the prize is significant and the national interest clear. We will never stoop to the tactics of our opponents. But we must seek to outplay them. In every domain. In every way. So intelligence must drive action. Action must deliver advantage. And advantage must serve Britain’s security and prosperity. But at the core, our deeper contribution is also our simplest – how we unlock human agency. Our fast-paced, tech and threat-infused world now generates more heat than light. As nations retrench and rearm, we are losing opportunities to listen to what’s really going on. I’ve seen time and again throughout my career, that this is where MI6 matters most: we listen and we hear. We understand, because we take time to learn languages and cultures, complex technical and historical detail, immerse ourselves in what’s really driving the situation. Across the globe, right now, our officers are finding people with the courage to step forward, and they are taking time to sit and listen to break these tightening cycles of violence. They listen for nuance, for connection, for opportunity. Over the years, I’ve listened to terrorists who have told us how to defuse the bomb because they know that more violence won’t help. To proliferators and smugglers who’ve told us where to find the dangerous material, motivated to protect their children’s future. To people trapped in authoritarian regimes who know, deep down, that their humanity is being chipped away – and that telling us what’s really going on is an important release, allowing us all to find better ways to navigate our changing world. So, we will work with our agents. And we will continue to engage directly, and with respect, with states and organisation currently working against us. Away from the glare of the media, we will use MI6’s convening power wherever we can to make a material difference, bringing parties together to defuse tensions. But the response to the increasing risks we face won’t be delivered by the UK intelligence community alone. Wider society has a role to play too. That includes work taking place in schools across the country so our children don’t get duped by information manipulation. Let’s all check sources, consider evidence, and be alive to those algorithms that trigger intense reactions, like fear. It also means everyone in society really understanding the world we are in – a world where terrorists plot against us, where our enemies fearmonger, bully and manipulate, and the front line is everywhere. Online, on our streets, in our supply chains, in the minds and on the screens of our citizens. We must all stand together against this. As we do today with our friends in Australia after the shocking antisemitic terrorist attack this weekend. My thoughts -and those of my whole organisation – are with the family, friends and loved ones of the victims. Light will always win over darkness. In rising to meet these challenges we, in MI6, will remain anchored to our values: courage, creativity, respect and integrity. And to our principles: accountability and trust are not constraints on our work; they are the foundations of our legitimacy with the British public. Recently, I had the privilege of meeting and thanking a foreign agent who has worked with us for decades, taking extraordinary risks to help keep the UK safe. I asked why. They said simply, ‘Your values. Your integrity and respect. None of us have a future without them’. This moment reinforced to me that we must remain a very human agency. And so, to sustain that trust, MI6 will continue to be more open. Not for the sake of visibility, but because it matters – and as my MI5 counterpart Sir Ken McCallum said recently - because it is a strength. We will continue the practice of speaking publicly, broaden our channels of engagement, and sustain our focus on attracting the most diverse talent to join our Service. Transparency does not mean revealing what must remain secret. It means showing the British people who we are, what we stand for, and why our work matters. We need your trust and support for the difficult and often dangerous work our agents pursue, every day of the year. In an age of uncertainty, one constant remains: the choices made by human beings still determine the shape of the world. Yes, technology can illuminate possibilities: but information requires judgement; complexity demands clarity; and only people can decide which path to follow. The United Kingdom’s global voice has never rested solely on strength – it has rested on trust, principle, and the ability to understand others as well as ourselves. That is also the essence of intelligence: not simply knowing the world, but interpreting it through a uniquely human lens. Ours is the quiet service, the hidden service. It is one rooted in a profound belief that when human beings act with purpose and integrity, they can steady a faltering world. When the Berlin Wall fell, it was our shared belief in freedom that carried Europe forward. When acts of terror targeted open societies, it was intelligence, cooperation and resolve that preserved them. And when adversaries blur fact and falsehood, our task is to defend the space where truth can still stand. As we step into the future, the tools at our disposal will evolve. But what will always matter most is the human element – the person who stands in the shadows and says: this is right, and that is wrong. That choice – the exercise of human agency – has shaped our world before, and it will shape it again. Because in the end, it is not what we can do that defines us, but what we choose to do. Thank you. Published 15 December 2025

John Sweeney

42,257 views • 9 months ago

🧬 The Recipe: How One Ovarian Cancer Trial Rebuilds the Immune System the Disease Switched Off A node-by-node case for durable immunity in the cancer that has resisted checkpoint blockade $NWBO and its #DCVax dendritic-cell platform sit at the heart of a new front-line #OvarianCancer trial, the same instructor-cell technology now aimed at the cancer that checkpoint blockade has barely touched. Advanced ovarian cancer kills more women than any other gynecologic malignancy, and it has shrugged off the #immunotherapy revolution almost entirely. Checkpoint blockade on its own reaches an objective response rate near eight percent in this disease, the figure from the $MRK #KEYNOTE-100 trial. The tumors are cold, the mutational burden is low, and the peritoneal cavity is a suppressive field that shuts an immune attack down before it can start. Two decades of single-agent vaccines and single-agent checkpoint drugs have not changed the survival math. Most patients respond to first-line chemotherapy and then relapse, and once the disease returns, the odds turn hard against them. For the patient living that diagnosis, a durable response is the only outcome that counts, and that is the one thing the field has not delivered. A Phase 2 trial opening at #UPMC Hillman in the second half of 2026, #NCT07634094, takes a different route. It does not add one more drug to the pile and hope. It treats ovarian cancer as one clinical face of a single, definable failure, and it rebuilds the broken machinery one node at a time. The sponsors are Pawel Kalinski MD PhD, $NWBO and $AIM. Here is the full logic, and why it is built to produce a response that lasts. 🔒 The hidden lesion: a silencing cascade Ovarian tumors run a self-reinforcing program that switches off the immune system's command center. It starts with chronic inflammation. Senescence-associated secretions and prostaglandin E2, the product of the COX-2 enzyme, keep the signaling protein STAT3 locked on. Persistent STAT3 pulls the silencing enzymes DNMT1 and EZH2 onto a single master gene, IRF8. That gene is the identity switch for the type 1 conventional dendritic cell, the cDC1, the one cell that licenses killer T cells with bioactive Silence IRF8 and the instructor disappears. With it gone, the tumor secretes decoy chemokines that recruit regulatory T cells, killer cells never receive their orders, and the disease grows in immunological darkness. This is not a quirk of ovarian cancer. The same cascade shows up in chronic infection and in aging tissue. Ovarian cancer is one face of a convergent mechanism, which is why a fix that works here points well beyond it. 🔄 The recipe: the cascade run in reverse Every component of the regimen corrects one node of that cascade. Pull out any single arm and the suppression reasserts itself through the others. That is what separates this from a kitchen sink: each part is load-bearing. · Celecoxib lifts the upstream PGE2 brake that keeps the silencing signal switched on. · Autologous, tumor-loaded alpha-DC1 supplies the instructor function from outside the silencing field, loaded with the whole tumor. This is the rebuilt command center the disease erased. · #rintatolimod, the selective TLR3 agonist marketed as #Ampligen, plus interferon-alpha flips the chemokine code tumor-selectively, from the CCL22 that recruits regulatory cells to the CXCL10 and CCL5 that pull in killers. #Bioferon · The alpha-DC1 program imprints CXCR3 and CCR5 homing receptors on the instructed CD8 cells, so they reach the tumor instead of circulating uselessly. · Cisplatin raises stress ligands so the killers can destroy low-antigen escape variants through the DNAM-1 and NKG2D receptors, closing the door on the engine of recurrence. · Paclitaxel plus the interferons repolarize suppressive M2 macrophages back to the supportive M1 state. · $MRK #Keytruda, releases the PD-1 brake last, only after the tumor has been made hot. The order is not cosmetic. The checkpoint comes last for a reason that most combination trials get wrong. 🔗 Why the combination is required, not additive Checkpoint blockade does not activate killer T cells by itself. Published work shows that anti-PD-1 efficacy depends on dendritic cells producing IL-12 inside the tumor (Garris, Immunity 2018). If the instructor is silenced and no IL-12 is being made, pembrolizumab has nothing to set loose. It is releasing a brake on a car with no engine. So restoring the IL-12 signal is the precondition for the checkpoint to do anything in this disease, not an optional add-on to it. The alpha-DC1 vaccine rebuilds the engine. Pembrolizumab takes the brake off. Neither delivers without the other. The relationship is causal, and that is the single idea the whole regimen is organized around. ⏳ Why the response should last A response that fades is not a cure, and durability is engineered here on four fronts at once. · Breadth. The vaccine is loaded with the whole tumor, not a single antigen, so the immune system learns the entire target and the tumor cannot escape by dropping one marker. · A lowered killing threshold. The DNAM-1 and NKG2D signals let killers finish variants that have shed antigen, while the requirement for true tumor recognition is preserved, so normal tissue is passed over. · Memory programming. Bioactive IL-12p70 does what ordinary dendritic-cell expansion cannot. It programs a self-renewing, TCF1-positive stem-like CD8 reservoir, the very population that predicts lasting benefit from checkpoint blockade (Goswami, Clinical Cancer Research 2025). · A self-reinforcing organ. Restored type 1 signaling matures tertiary lymphoid structures inside the tumor, the local factories from which durable immunity is rebuilt long after the last dose. 📊 Already partly de-risked This is not a first guess. The chemokine-and-checkpoint backbone was already tested in recurrent platinum-sensitive ovarian cancer in trial NCT03734692: intraperitoneal cisplatin plus rintatolimod plus pembrolizumab. That study produced an objective response rate near fifty percent, several times the roughly eight percent checkpoint blockade reaches alone in $MRK #KEYNOTE-100, accompanied by the exact chemokine shift the model predicts, the rise in CXCL9, CXCL10, and CXCL11 that a restored type 1 program produces. $MRK collaborated on it and supported it, and the final primary endpoint reported in May 2026. #SITC26 #ASCO26 The new trial adds the missing piece, the alpha-DC1 instructor whose intellectual property traces to #RoswellPark, and moves the whole regimen to the front line, where the tumor is largest and the antigen supply is richest. It is the same spine, established in recurrent disease, now armed with the one component that was absent. 🔬 A trial built to be read, not just won NCT07634094 enrolls twenty-eight patients with Stage III to IV epithelial ovarian, tubal, or peritoneal cancer, chemo-naive, in the neoadjuvant #neoadjuvant setting. #OvarianCancerAwareness #gyncsm #BRCA Treating before surgery buys the cleanest possible readout: the resected tumor itself. The co-primary endpoints are the safety of the full combination and pathologic complete response at debulking. A pathologic complete response, meaning no viable tumor left in the surgical specimen, is one of the most demanding endpoints in solid-tumor #oncology and a recognized marker of long-term benefit. The design also reads the mechanism directly. It looks for the chemokine switch, the rise in intratumoral CD8 cells with a favorable ratio to regulatory cells and a TCF1-positive phenotype, the falling inflammatory tone, and the specific signature of restored pulsed IL-12p70 against preserved bulk IL-12. The study is built to show whether the mechanism engaged, not only whether tumors shrank. Enrollment is expected to begin in the second half of 2026, and because the central readout is the surgical specimen rather than years of follow-up, the first mechanistic signals should arrive relatively early. 🏭 Why this is a platform, not a one-off The instructor cell at the center of this regimen is the same dendritic-cell platform Northwest Biotherapeutics has built its company around. #DCVax extended survival in Phase 3 glioblastoma (JAMA Oncology, 2023), and a UK marketing application is pending with MHRAgovuk. The same approach has already worked in ovarian cancer. At the University of Pennsylvania, a personalized whole-tumor dendritic-cell vaccine in recurrent ovarian cancer was well tolerated and induced broad antitumor T-cell responses that tracked with significantly longer survival, with two-year survival of one hundred percent in the immune responders against twenty-five percent in non-responders (Tanyi et al., Science Translational Medicine, 2018). Those dendritic cells were loaded with the patient's own whole tumor and activated toward the same type 1 program this regimen rebuilds. That is the proof of principle, and this trial is the more complete version of it. The dendritic cell here is engineered for higher, sustained IL-12p70. It is given in the front line, where the antigen supply is richest, rather than in heavily pretreated relapse. The suppressive microenvironment is reprogrammed in parallel rather than left intact, and the checkpoint is released at the end. The Penn vaccine carried the immune response largely on its own. This regimen clears the field for it first, then takes the brake off. The historical knock on personalized cell therapy was manufacturing: bespoke, hand-built, hard to scale. Northwest Biotherapeutics has been answering that directly. #Flaskworks #EDEN, the closed, automated manufacturing system the company acquired, standardizes production and removes the single-site hand manufacturing that limited earlier programs. The Sawston facility #Sawston in the UK, operated by #AdventBioServices, a wholly owned Northwest Biotherapeutics subsidiary, under MHRA good-manufacturing standards, is bringing its first Grade C suite online in 2026, a step anticipated to more than double capacity, with a dedicated leukapheresis clinic already running. The company has also added senior leadership to drive the platform, naming the biopharmaceutical veteran Dr. Annalisa Jenkins as a strategic adviser. The consequence is concrete. If the mechanism reads out in the resected tumor, the system that delivers it is already being built to scale, across the many solid tumors that run the same silencing cascade. One trial, read correctly, does not validate a single drug. It tests a repeatable way of rebuilding antitumor immunity. That reach is the point. The same instructor sits at the center of the silencing cascade across most solid tumors, which is why the dendritic-cell platform is framed around the approach itself rather than a single indication. A front-line ovarian readout that confirms the mechanism would be evidence for the method, not for one tumor type alone. The needle moves on the tissue, not on the thesis, and no paragraph substitutes for the pathology report. What the design offers is a complete, testable mechanism for durable immunity in ovarian cancer, paired with a manufacturing system already capable of producing it at scale. The readout in the resected tumor will speak for itself. Not financial advice. Do your own research. #DCVaxForBraelyn

🧬 The Recipe: How One Ovarian Cancer Trial Rebuilds the Immune System the Disease Switched Off A node-by-node case for durable immunity in the cancer that has resisted checkpoint blockade $NWBO and its #DCVax dendritic-cell platform sit at the heart of a new front-line #OvarianCancer trial, the same instructor-cell technology now aimed at the cancer that checkpoint blockade has barely touched. Advanced ovarian cancer kills more women than any other gynecologic malignancy, and it has shrugged off the #immunotherapy revolution almost entirely. Checkpoint blockade on its own reaches an objective response rate near eight percent in this disease, the figure from the $MRK #KEYNOTE-100 trial. The tumors are cold, the mutational burden is low, and the peritoneal cavity is a suppressive field that shuts an immune attack down before it can start. Two decades of single-agent vaccines and single-agent checkpoint drugs have not changed the survival math. Most patients respond to first-line chemotherapy and then relapse, and once the disease returns, the odds turn hard against them. For the patient living that diagnosis, a durable response is the only outcome that counts, and that is the one thing the field has not delivered. A Phase 2 trial opening at #UPMC Hillman in the second half of 2026, #NCT07634094, takes a different route. It does not add one more drug to the pile and hope. It treats ovarian cancer as one clinical face of a single, definable failure, and it rebuilds the broken machinery one node at a time. The sponsors are Pawel Kalinski MD PhD, $NWBO and $AIM. Here is the full logic, and why it is built to produce a response that lasts. 🔒 The hidden lesion: a silencing cascade Ovarian tumors run a self-reinforcing program that switches off the immune system's command center. It starts with chronic inflammation. Senescence-associated secretions and prostaglandin E2, the product of the COX-2 enzyme, keep the signaling protein STAT3 locked on. Persistent STAT3 pulls the silencing enzymes DNMT1 and EZH2 onto a single master gene, IRF8. That gene is the identity switch for the type 1 conventional dendritic cell, the cDC1, the one cell that licenses killer T cells with bioactive Silence IRF8 and the instructor disappears. With it gone, the tumor secretes decoy chemokines that recruit regulatory T cells, killer cells never receive their orders, and the disease grows in immunological darkness. This is not a quirk of ovarian cancer. The same cascade shows up in chronic infection and in aging tissue. Ovarian cancer is one face of a convergent mechanism, which is why a fix that works here points well beyond it. 🔄 The recipe: the cascade run in reverse Every component of the regimen corrects one node of that cascade. Pull out any single arm and the suppression reasserts itself through the others. That is what separates this from a kitchen sink: each part is load-bearing. · Celecoxib lifts the upstream PGE2 brake that keeps the silencing signal switched on. · Autologous, tumor-loaded alpha-DC1 supplies the instructor function from outside the silencing field, loaded with the whole tumor. This is the rebuilt command center the disease erased. · #rintatolimod, the selective TLR3 agonist marketed as #Ampligen, plus interferon-alpha flips the chemokine code tumor-selectively, from the CCL22 that recruits regulatory cells to the CXCL10 and CCL5 that pull in killers. #Bioferon · The alpha-DC1 program imprints CXCR3 and CCR5 homing receptors on the instructed CD8 cells, so they reach the tumor instead of circulating uselessly. · Cisplatin raises stress ligands so the killers can destroy low-antigen escape variants through the DNAM-1 and NKG2D receptors, closing the door on the engine of recurrence. · Paclitaxel plus the interferons repolarize suppressive M2 macrophages back to the supportive M1 state. · $MRK #Keytruda, releases the PD-1 brake last, only after the tumor has been made hot. The order is not cosmetic. The checkpoint comes last for a reason that most combination trials get wrong. 🔗 Why the combination is required, not additive Checkpoint blockade does not activate killer T cells by itself. Published work shows that anti-PD-1 efficacy depends on dendritic cells producing IL-12 inside the tumor (Garris, Immunity 2018). If the instructor is silenced and no IL-12 is being made, pembrolizumab has nothing to set loose. It is releasing a brake on a car with no engine. So restoring the IL-12 signal is the precondition for the checkpoint to do anything in this disease, not an optional add-on to it. The alpha-DC1 vaccine rebuilds the engine. Pembrolizumab takes the brake off. Neither delivers without the other. The relationship is causal, and that is the single idea the whole regimen is organized around. ⏳ Why the response should last A response that fades is not a cure, and durability is engineered here on four fronts at once. · Breadth. The vaccine is loaded with the whole tumor, not a single antigen, so the immune system learns the entire target and the tumor cannot escape by dropping one marker. · A lowered killing threshold. The DNAM-1 and NKG2D signals let killers finish variants that have shed antigen, while the requirement for true tumor recognition is preserved, so normal tissue is passed over. · Memory programming. Bioactive IL-12p70 does what ordinary dendritic-cell expansion cannot. It programs a self-renewing, TCF1-positive stem-like CD8 reservoir, the very population that predicts lasting benefit from checkpoint blockade (Goswami, Clinical Cancer Research 2025). · A self-reinforcing organ. Restored type 1 signaling matures tertiary lymphoid structures inside the tumor, the local factories from which durable immunity is rebuilt long after the last dose. 📊 Already partly de-risked This is not a first guess. The chemokine-and-checkpoint backbone was already tested in recurrent platinum-sensitive ovarian cancer in trial NCT03734692: intraperitoneal cisplatin plus rintatolimod plus pembrolizumab. That study produced an objective response rate near fifty percent, several times the roughly eight percent checkpoint blockade reaches alone in $MRK #KEYNOTE-100, accompanied by the exact chemokine shift the model predicts, the rise in CXCL9, CXCL10, and CXCL11 that a restored type 1 program produces. $MRK collaborated on it and supported it, and the final primary endpoint reported in May 2026. #SITC26 #ASCO26 The new trial adds the missing piece, the alpha-DC1 instructor whose intellectual property traces to #RoswellPark, and moves the whole regimen to the front line, where the tumor is largest and the antigen supply is richest. It is the same spine, established in recurrent disease, now armed with the one component that was absent. 🔬 A trial built to be read, not just won NCT07634094 enrolls twenty-eight patients with Stage III to IV epithelial ovarian, tubal, or peritoneal cancer, chemo-naive, in the neoadjuvant #neoadjuvant setting. #OvarianCancerAwareness #gyncsm #BRCA Treating before surgery buys the cleanest possible readout: the resected tumor itself. The co-primary endpoints are the safety of the full combination and pathologic complete response at debulking. A pathologic complete response, meaning no viable tumor left in the surgical specimen, is one of the most demanding endpoints in solid-tumor #oncology and a recognized marker of long-term benefit. The design also reads the mechanism directly. It looks for the chemokine switch, the rise in intratumoral CD8 cells with a favorable ratio to regulatory cells and a TCF1-positive phenotype, the falling inflammatory tone, and the specific signature of restored pulsed IL-12p70 against preserved bulk IL-12. The study is built to show whether the mechanism engaged, not only whether tumors shrank. Enrollment is expected to begin in the second half of 2026, and because the central readout is the surgical specimen rather than years of follow-up, the first mechanistic signals should arrive relatively early. 🏭 Why this is a platform, not a one-off The instructor cell at the center of this regimen is the same dendritic-cell platform Northwest Biotherapeutics has built its company around. #DCVax extended survival in Phase 3 glioblastoma (JAMA Oncology, 2023), and a UK marketing application is pending with MHRAgovuk. The same approach has already worked in ovarian cancer. At the University of Pennsylvania, a personalized whole-tumor dendritic-cell vaccine in recurrent ovarian cancer was well tolerated and induced broad antitumor T-cell responses that tracked with significantly longer survival, with two-year survival of one hundred percent in the immune responders against twenty-five percent in non-responders (Tanyi et al., Science Translational Medicine, 2018). Those dendritic cells were loaded with the patient's own whole tumor and activated toward the same type 1 program this regimen rebuilds. That is the proof of principle, and this trial is the more complete version of it. The dendritic cell here is engineered for higher, sustained IL-12p70. It is given in the front line, where the antigen supply is richest, rather than in heavily pretreated relapse. The suppressive microenvironment is reprogrammed in parallel rather than left intact, and the checkpoint is released at the end. The Penn vaccine carried the immune response largely on its own. This regimen clears the field for it first, then takes the brake off. The historical knock on personalized cell therapy was manufacturing: bespoke, hand-built, hard to scale. Northwest Biotherapeutics has been answering that directly. #Flaskworks #EDEN, the closed, automated manufacturing system the company acquired, standardizes production and removes the single-site hand manufacturing that limited earlier programs. The Sawston facility #Sawston in the UK, operated by #AdventBioServices, a wholly owned Northwest Biotherapeutics subsidiary, under MHRA good-manufacturing standards, is bringing its first Grade C suite online in 2026, a step anticipated to more than double capacity, with a dedicated leukapheresis clinic already running. The company has also added senior leadership to drive the platform, naming the biopharmaceutical veteran Dr. Annalisa Jenkins as a strategic adviser. The consequence is concrete. If the mechanism reads out in the resected tumor, the system that delivers it is already being built to scale, across the many solid tumors that run the same silencing cascade. One trial, read correctly, does not validate a single drug. It tests a repeatable way of rebuilding antitumor immunity. That reach is the point. The same instructor sits at the center of the silencing cascade across most solid tumors, which is why the dendritic-cell platform is framed around the approach itself rather than a single indication. A front-line ovarian readout that confirms the mechanism would be evidence for the method, not for one tumor type alone. The needle moves on the tissue, not on the thesis, and no paragraph substitutes for the pathology report. What the design offers is a complete, testable mechanism for durable immunity in ovarian cancer, paired with a manufacturing system already capable of producing it at scale. The readout in the resected tumor will speak for itself. Not financial advice. Do your own research. #DCVaxForBraelyn

Andrew Caravello, DO

10,459 views • 3 months ago