Monthly Archives: May 2020

A study led by researchers at the Babraham Institute in collaboration with the Wellcome Sanger Institute has uncovered how variations in a non-protein coding dark matter region of the genome could make patients susceptible to complex autoimmune and allergic diseases such as inflammatory bowel disease. The study in mice and human cells reveals a key genetic switch that helps immune responses remain in check. Published in Nature, the research, involving collaborations with research institutions in the UK and worldwide, identified a new potential therapeutic target for the treatment of inflammatory diseases.Over the last twenty years, the genetic basis of susceptibility to complex autoimmune and allergic diseases, such as Crohns disease, ulcerative colitis, type 1 diabetes and asthma, has been narrowed down to a particular region of chromosome 11. This work has involved large scale genome-wide association studies (GWAS), a genome-wide spot-the-difference comparison between the genomes of individuals with or without a disease, to highlight regions of variation in the DNA code. This can identify potential genetic causes, and reveal possible drug targets.

However, most of the genetic variations responsible for the susceptibility to complex immune and allergic diseases are concentrated within regions of the genome that dont encode proteins the genomes dark matter. This means theres not always a clear gene target for further investigation and the development of treatments.

Recent advances in sequencing-based approaches have shown that these disease-associated genetic changes are concentrated within regions of DNA called enhancers, which act as switches to precisely regulate the expression of genes. Further technological developments have allowed scientists to map physical interactions between different remote parts of the genome in 3D, so they can connect enhancers in non-coding regions with their target gene.

To gain insight into inflammatory disease, a large team of researchers used these methods to study an enigmatic non-protein-coding region of the genome whose genetic variations are associated with increased immune disease risk. They identified an enhancer element that is required for the immune systems peace-keepers and immune response mediators, regulatory T cells (Tregs), to balance an immune response.

Lead researcher and Babraham Institute group leader, Dr Rahul Roychoudhuri said: The immune system needs a way of preventing reactions to harmless self- and foreign substances and Treg cells play a vital role in this. Theyre also crucial in maintaining balance in the immune system, so that our immune responses are kept in check during infections. Tregs only represent a small percentage of the cells making up our complete immune system but theyre essential; without them we die from excessive inflammation. Despite this important role, there has been little evidence that unequivocally links the genetic variations that cause certain individuals to be susceptible to inflammatory diseases to changes in Treg function. It turns out that non-protein-coding regions provided us with the opportunity to address this important question in the field.

Evolution gave the researchers a helping hand. The researchers took advantage of an approach called shared synteny, where not just genes are conserved between species, but a whole section of the genome. Similar to finding part of your book collection duplicated in your neighbors house, including the order of their arrangement on the bookshelf.

They used this genomic similarity to translate what was known about the enhancer in the human genome and find the corresponding region in mice. They then explored the biological effect of removing the enhancer using mouse models.

The researchers found that the enhancer element controls the expression of a gene in Treg cells, which encodes a protein called GARP (Glycoprotein A Repetitions Predominant). They showed that deleting this enhancer element caused loss of the GARP protein in Treg cells, and an uncontrolled response to a triggered inflammation of the colon lining. This demonstrated that the enhancer is required for Treg-mediated suppression of colitis, with a role for the GARP protein in this immune system control.

There was a similar effect in human Treg cells from healthy blood donors. The researchers identified an enhancer region whose activity was impacted by genetic variation specifically in Treg cells. The enhancer directly interacted with the human form of the same gene, and the genomic variations occurring in the enhancer element were associated with reduced GARP expression.

Dr Gosia Trynka, a senior author on the paper from the Wellcome Sanger Institute and Open Targets, said: Genetic variation provides important clues into disease processes that can be targeted by drugs. In our joint efforts here, we combined human and mouse research to gain invaluable insight into complex processes underlying immune diseases. This has identified GARP as a promising new drug target and brings us a step closer to developing more efficient therapies for people suffering from diseases such as asthma or inflammatory bowel disease.

Dr Roychoudhuri concludes: Decades of research have now identified the variations in our genomes that make some of us more susceptible to inflammatory diseases than others. It has been very difficult, however, to make sense of how these variations relate to immune disease since many of them occur in non-protein-coding regions, and therefore the implications of these changes are poorly understood. Studies such as these will enable us to link the genetic switches that commonly reside in such disease-associated non-coding regions with the genes they control in different cell types. This will yield new insights into the cell types and genes underlying disease biology and provide new targets for therapeutic development.ReferenceNasrallahet al. (2020). A distal enhancer at risk locus 11q13.5 promotes suppression of colitis by Treg cells. Nature. DOI: https://doi.org/10.1038/s41586-020-2296-7

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How "Dark Matter" Regions of the Genome Affect Inflammatory Diseases - Technology Networks

LONDON The U.K. is launching a 28 million (US$34.5 million) project to sequence the whole genome of every COVID-19 patient in the country treated in intensive care, with the aim of uncovering host genetic factors that lead some people to be more severely affected by the infection.

The study will involve up to 20,000 people currently or previously treated in one of 170 intensive care units (ICUs), whose genomes will be compared to 15,000 people with a confirmed infection who had mild or moderate symptoms.

It was evident from the first cases in China that people with co-morbidities experience more severe illness, but patients with the same underlying conditions have been found to respond very differently. While co-morbidities and factors such as age and obesity are important, it is thought this high variability in the severity of COVID-19 infections is linked to underlying genetic factors that influence response to the virus.

Backed by detailed medical records, the study will explore the spectrum of symptoms and attempt to pinpoint their genetic roots. The findings will provide biomarkers for assessing in advance which patients will react badly, help inform treatment with existing drugs and provide de novo targets.

This large-scale whole genome sequencing project is not beginning from a standing start, but builds on Genomicc (Genetics Of Mortality In Critical Care), launched in 2016, to sequence the genomes of patients with any condition who were so ill they required critical care.

To date, DNA samples have been collected from patients who were critically ill with influenza, SARS-CoV-1, MERS, sepsis and other causes.

With over 2,000 patients recruited, it is by far the largest study of critical care genetics in the world, said Kenneth Baillie, academic consultant in critical care at Edinburgh University and principal investigator. In total, we have 2,133 cases in Genomicc, but no results yet for COVID-19, he told BioWorld.

To date, Genomicc has been funded by a sepsis charity; the U.K. government funding and the urgency behind all COVID-19 research will accelerate the study.

Genomicc also will have the backing of Genomics England, the not-for-profit government funded company which has been working on translating advances in genomics into clinical practice.

So far, that work has focused on delivering genetic diagnoses for rare disease patients and selecting gene-targeted therapies in cancer, but Mark Caulfield, chief scientific officer, said Genomics Englands expertise can be applied to understanding why the virus is life-threatening for some, while others have a mild infection. By reading the whole genome, we may be able to identify variation that affects response to COVID-19 and discover new therapies, he said.

Genomics England is now recruiting volunteers who have been ill with COVID-19 to take part in the study. All of 35,000 COVID-19 genomes will be sequenced by Illumina Inc., which will share some of the costs via an in-kind contribution.

Focus on susceptibility

Baillies research into the genomes of critically ill patient builds on the observation that the cause of death following a serious infection is often not attributable to the direct impact of the pathogen or any toxin it produces, but a consequence of a systemic immune response.

Exploring the genetic underpinnings of that is one source of drug targets. A second source will be in identifying host factors the virus depends on for replication. In research published in January, Baillie and colleagues reported the results of a wide-scale screen in which they identified 121 host genes that are required for influenza A replication.

In a hugely heterogeneous disease, the large-scale sequencing of whole genome sequences is the best way to track down the factors underlying the spectrum of response to COVID-19 infection, Baillie said. I think this is one of the best ways to tackle this question. By focusing on extreme susceptibility, that is, patients with critical illness caused by COVID-19, we can increase the size of effect that we see for any genetic signals, making them easier to find, he said.

One very striking characteristic of people who suffer the worst effects of COVID-19 is that far more of them are men than women. Baillie said, It may well be that [Genomicc] gives us clues to explain the difference in susceptibility between the sexes.

Part of the overall study will focus on children and young adults with no known underlying health problems who have been severely affected by COVID-19. There have been reports that a very small number of children in the U.K., U.S. and Italy developed a significant multisystem inflammatory response associated with COVID-19.

The power of the COVID-19 whole genome sequence data will be amplified by linking it to virus genome data. Worldwide, the repository of viral sequences from patients now numbers tens of thousands. In the U.K., the COVID-19 Genomics UK (COG-UK) consortium has sequenced more than 10,000 virus genomes, meaning it will be possible to put together matched pairs of viral/patient genomes.

Linking [viral sequence] data to the patients own genome data in the Genomicc study may provide unique insights into how patient and virus genomes act together to influence the patients response to the infection, said Sharon Peacock, director of COG-UK.

The program is significant for many reasons not only to provide insights into the cause of the potential role of human genome in the severity of COVID-19, but also to provide a real opportunity to link other similar datasets globally, Naveed Aziz, chief administrative and scientific officer at CGEN, Canadas national genome sequencing and analysis platform, told BioWorld.

For example, the Canadian HostSeq program aims to sequence genomes of 10,000 COVID-19 positive people. The ability to query a larger dataset from across the globe will allow researchers to increase the power of COVID-19-related studies when it comes to investigating human gene variations associated with the immune response against infection by SARS-CoV-2, Aziz said.

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U.K. genome sequencing project aims to identify genetic links to severe COVID-19 infection - BioWorld Online

Abstract / Synopsis:

Quantitative polymerase chain reaction and whole genome sequencing contribute to pathogen identification in endophthalmitis.

Worse outcomes after development of endophthalmitis postoperatively are associated with the presence of bacteria and higher bacterial loads of pathogens other than Staphylococcus epidermidis as detected by whole-genome sequencing (WGS) and quantitative polymerase chain reaction (qPCR).

The incidence rate of endophthalmitis that develops after intravitreal injections is low, but more and more injections are being administered annually in the US and the rate of endophthalmitis is climbing.

However, the current gold standard, cultures, seems less than adequate, in that the Endophthalmitis Vitrectomy Study (Arch Ophthalmol. 1995;113:1479-96) found that only 69.3% of cases were culture-positive, leaving the rest with no etiologic diagnosis.

Related: Diagnostic advances offer glimpse of endophthalmitis pathogens

In addition, the culture-positive rates may be even lower in endophthalmitis that develops following intravitreal injections, in that among 23 cases of endophthalmitis analyzed following 27,736 injections, 16 cases were found to be culture-negative (Ophthalmology. 2011;118:2028-34).

According to Cecilia Lee, MD, MS, and colleagues, as the prognosis of endophthalmitis appears at least partially dependent on the causative organism, the high rate of culture-negative cases suggests a need for a more sensitive modality for pathogen detection.

In light of this, Dr. Lee and colleagues conducted a prospective cohort study in which MidAtlantic Retina, the Retina Service of Wills Eye Hospital, Philadelphia, and the University of Washington, Seattle, participated.

Consecutive patients were enrolled who had a clinical diagnosis of endophthalmitis after any intraocular procedure or surgery within 6 weeks of presentation. The day that they were recruited into the study, all patients underwent either intraocular fluid biopsy or pars plana vitrectomy. qPCR for specific pathogens and WGS were performed, the investigators recounted.

Related: Small changes can help beat endophthalmitis bug

Study findingsFifty patients (52% men; mean age, 72 years) were enrolled in the study. Following qPCR and WGS, 24 cases were culture-positive and the remainder culture-negative. WGS identified the cultured organism in 76% of the culture-positive cases and identified potential pathogens in 33% of the culture-negative cases, said Dr. Lee, who is from the Department of Ophthalmology, University of Washington, Seattle. They published their findings on behalf of the Endophthalmitis Study Group in the American Journal of Ophthalmology. (2020; doi: https://doi.org/10.1016/j.ajo.2020.03.008.)

The most frequently cultured organisms were S. epidermidis followed by other Staphylococcus and Streptococcus species.

Regarding bacterial load, the median load was 3.32 (mean, 53.50; range, 0.028-480) in the culture-positive cases. In the WGS-positive but culture-negative cases, the median bacterial load was 1.44 (mean, 2.04; range, 0.35-6.19).

The visual outcomes in cases with S. epidermidis endophthalmitis did not differ from the visual outcomes in cases that were pathogen-negative; however, the patients who tested positive for organisms other than S. epidermidis had worse visual outcomes.

Related: Study targets therapies for endophthalmitis

The investigators found that in cases that had higher baseline bacterial DNA loads of pathogens other than S. epidermidis that were detected by WGS had worse visual acuity levels at months 1 and 3. Interestingly, the bacterial loads of S. epidermidis did not seem to affect the outcomes, the investigators reported.

qPCR identified Torque teno virus in 49% of cases and Merkel cell polyomavirus in 19% of cases. When Torque teno virus was present, there was a higher rate of secondary pars plana vitrectomy and retinal detachment.

The authors concluded that the culture/molecular pathogen testing status (for bacteria and virus) as well as the baseline visual acuity has prognostic significance for clinical outcomes including the visual acuity and secondary vitrectomy in endophthalmitis.

Molecular studies provide more extensive and sensitive characterization of pathogens and have the potential to allow for improved treat paradigms, they wrote. Further development of rapid, point-of-service molecular diagnostics and subsequent prospective randomized controlled clinical trials will allow for testing of new paradigms for risk stratification and individualized treatment for endophthalmitis.

Read more by Lynda Charters

Cecilia Lee, MD, MSE: [emailprotected]Dr. Lee has no financial interest in the subject of this report.

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Endophthalmitis detection by whole genome sequencing and qPCR - Ophthalmology Times

Subject: Mainframes to PCs. $1B genome to $1k. The brain and mind are next.

Hello Humanity,

What a fun week it has been! After four years quietly building, we pulled back the curtains at Kernel, revealing how our brain recording hardware will replace room-sized machines.

Weve seen this before. Mainframes became PCs. The $1B genome became $1k. The brain and mind are next.

We also showed a fun demonstration: Kernel Sound ID, which decodes a persons brain activity and within seconds identifies the speech or song they are hearing. Here is the science.

So, where do we go from here? Unlike our steps, calories, likes and followers, the technology hasnt yet existed to meaningfully quantify our brains and minds in natural environments and at scale. The inner workings of the most complicated and consequential organ on the planet remains a black boxbut not for long. Consider this:

We live in a data-illuminated world, but the user manual for our brains has no biomarkers. The current gold standard, Diagnostic and Statistical Manual of Mental Disorders (DSM), has not a single number. Leaving us with no option but to describe cognition in hunches, not numbers.

Imagine a cardiologist explaining how your heart is doing with hunches. No electrocardiogram (ECG). No blood work. Just asking you some questions about how your heart feels. We dont self-introspect to determine our cholesterol levels either.

When it comes to understanding our own and others brains and minds, we are in medieval times, stuck with self-introspection.

Of the little we can measure of our brain today, we build around it. For example, traffic signals are designed around a few measures, including the 1) limits of human reaction 2) physics of braking distance required and 3) needs of society, managing traffic flow. Blood-alcohol levels are another example we measure this because we care about what it means for a drivers impaired cognition.

However, we cannot yet quantify and characterize decision making, cooperation, emotion, attention, bias, or focus because we dont have the numbers. Instead, we make guesses and rely upon hunches and hopes.

What if we could do better? What would such a world look like?

If we could quantify and characterize thoughts and emotions, conscious and subconscious, a Neuro-Quantified Era (NQE) would emerge. The foundation already exists to use numbers judiciously.

Perhaps in an NQE there would be bumper lanes for decision making, enabling us to bowl more cognitive strikes and fewer gutter balls. In new(ish) cars, when you want to change lanes but someone is in your blind spot, you get a warning that you are about to err.

Could we do the same for certain anxieties, risks, or maladaptive thoughts? (There is already a stress relieving GPS app that directs people through rush hour traffic. Again, this is based on a crude cognitive proxy a hunch.)

In a NQE, how would humans cooperate during a pandemic? Or, how would we manage an existential crisis such as climate change.something that happens gradually and then all of a sudden, doesnt have dopamine feedback loops, and cant be perceived with the five senses? A trio that is especially lethal to humans.

Future generations may condemn us for our mindlessness in using our god-like technology powers to encourage lesser versions of ourselves (ie. digital addiction, extremism, misinformation.) Our cognitive biases have held us back for too long.

Maybe a neurome, like our genome, would give us a blueprint of insight and plan for action. Could we create the needed bridge between our technology, science and institutions to systematically and methodically scaffold human progress?

Coronavirus has reminded us that human nature is fundamentally unchanged from millennia ago. We may find ourselves wanting to revisit first principles of what it means to be human to improve whats not working.

Sometimes the worst events in life become the greatest learning moments.

Bryan

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Mainframes to PCs. $1B genome to $1k. The brain and mind are next. - TechCrunch

Understanding the origins of the virus causing COVID-19 is one of the key questions scientists are trying to resolve while working out how to manage the pandemic. But in a fast-evolving situation, we're bound to point our fingers at a few innocent suspects along the way.

The current hypothesis goes something like this: SARS-CoV-2 passed through a mystery animal host in its suspected evolutionary journey from bats to humans. Critically endangered pangolins have been a favoured candidate for this intermediary host, but now a genomic analysis led by geneticist Ping Liu from Guangdong Academy of Science in China has provided evidence this may not be the case.

SARS-CoV-2 belongs to the Betacoronavirus genus of coronaviruses; this group of coronaviruses primarily infects mammals, and the new study suggests that pangolins are indeed natural hosts for them.

The team pieced together almost an entire genome of the coronaviruses found in two sick Malayan pangolins (Manis javanica). They called the coronavirus isolated from these critically endangered animals pangolin-CoV-2020. Its final sequence had 29,521 base pairs, only slightly shorter than the 30,000-odd base pairs making up SARS-CoV-2.

The resulting genome displayed a 90.32 percent sequence similarity to SARS-CoV-2 and 90.24 percent to the Rhinolophus affinis bat coronavirus BatCoV-RaTG13, which still remains the closest known relative to SARS-CoV-2, with a match of 96.18 percent.

But the sequence similarities don't reflect the full story. The genetic instructions for the all-important protein spike of the SARS-CoV-2 virus matched more between the bat and human coronavirus than the pangolin one.

However, the pangolin virus essentially shares the same ACE2 binding receptor as that used by the COVID-19 virus - the part of the spike that allows the virus to enter and infect human cells. This was also found in another study that is still undergoing review, and led to suggestions that the human coronavirus may be a type of hybrid (a chimera) between a bat and a pangolin virus.

Liu's team also thinks these similarities may indicate that a recombination event occurred somewhere in the evolution of these different viruses - where the viral genomes exchanged pieces of their genetic materials with each other. However, their analysis of the evolutionary relationship between the three viruses did not support the idea that the human version evolved directly from the pangolin one.

"At the genomic level, SARS-CoV-2 was also genetically closer to Bat-CoV-RaTG13 than pangolin-CoV-2020," they wrote in their paper.

There are clearly still a lot of unknowns. With well over 4 million confirmed cases around the world, and a death toll still increasing sharply, the need to understand as much as we can about this virus just continues to intensify.

However, one thing all these genetics studies have firmly ruled out is the idea that the virus was lab made.

As for the pangolins, they had been rescued by the Guangdong Wildlife Rescue Center after being smuggled for black market trade, and sadly succumbed to their illness. Liu's team could not determine if their deaths were linked to the coronavirus they found.

But perhaps a little good can arise from all this, at least for the world's most trafficked mammal, with the researchers concluding:

"Minimising the exposures of humans to wildlife will be important to reduce the spillover risks of coronaviruses from wild animals to humans."

The new research was published in PLOS Pathogens.

Excerpt from:
Pangolins May Not Have Been The Intermediary Host of SARS-CoV-2 After All - ScienceAlert

Nafeez Ahmed explores the troubling implications and assumptions of the Governments AI-driven gene programme.

In Part 1 of this investigation, I looked at how the convergence of an AI Superstate and corporate interests with health data lies at the heart of a new frontier for profit and surveillance. But the Governments response during the COVID-19 pandemic has revealed something even more profoundly disturbing: a fascination with genomics which moves from a merely descriptive tool to something so prescriptive it verges on eugenics.

The NHSX app is simply one project with a questionable design which appears to result from the Governments much wider project to remake the NHS.

At the core of the new NHSX AI drive is the goal of predictive, preventive, personalised and participatory medicine, according to an NHSX document published in October 2019. Pivotal to this AI-driven transformation is genetics:

Key to unlocking the benefits of precision medicine with AI is the use of genomic data generated by genome sequencing. Machine learning is already being used to automate genome quality control. AI has improved the ability to process genomes rapidly and to high standards and can also now help improve genome interpretation.

The NHS Genomic Medicine Service is starting with a focus on cancer, rare and inherited diseases,but its broader goal is far more comprehensive. Initially, the hope is that genomics will expand to cover other areas, such as pharmacogenomics, which looks at how an individuals genes influence a particular biological process that mediates the effects of a medicine, according to The Pharmaceutical Journal.

But the end-goal is to convert the NHS into a health service oriented fundamentally around the role of genetics in disease. The aspiration is that from 2020, and by 2025, genomic medicine will be an embedded part of routine care to enable better prediction and prevention of disease and fewer adverse drug reactions. The GMS aims to complete five million genomic analyses and five million early disease cohorts over the next five years.

By 2025, genomic technologies will be embedded through multiple clinical pathways and included as a fundamental part of clinical training. As a result, it is hoped that there will be a new taxonomy of medicine based on the underlying drivers of disease.

But, this entire premise is deeply questionable. There is little evidence that the underlying drivers of disease are primarily genetic.

Last December, a study in the journal PLOS One found that genetics usually explains no more than 5-10% of the risk for several common diseases. The study examined data from nearly 600 earlier studies identifying associations between common variations in the DNA sequence and more than 200 medical conditions. But its conclusion was stark: more than 95% of diseases or disease risks including Alzheimers, autism, asthma, juvenile diabetes, psoriasis, and so on could not be predicted accurately from the DNA sequence. A separate meta-analysis of two decades of DNA science corroborated this finding.

The implication is startling: that the entire premise for the billions of pounds this Government is investing in building a new privatised NHS infrastructure for AI-driven genomic medicine is scientifically unfounded.

The obsession with genetics can be traced directly back to the Prime Ministers chief advisor, Dominic Cummings.

Cummings set out his vision for the NHS in a February 2019 blog, which although previously reported on has not been fully appreciated for its astonishingly direct implications. While focusing on disease risk, the blog flagged-up Cummings hopes that a new NHS genomics prediction programme would ultimately allow the UK to, not just prevent diseases, but to do so before birth in effect a nod toward the selective breeding techniques at the core of eugenics.

They are using the COVID-19 crisis to erect a corporate superstate powered by mass surveillance and AI. Their grim ambition is to reach into the very DNA of every British citizen.

His vision for what a genomics-focused NHS would look like bears startling resemblance to the core ideas of eugenics the discredited pseudoscience aiming to improve the genetic quality of a human population by selecting for superior groups and excluding those with inferior genes. Its worst manifestations were exemplified by the Nazis.

In the blog, Cummings wrote:

Britain could contribute huge value to the world by leveraging existing assets, including scientific talent and how the NHS is structured, to push the frontiers of a rapidly evolving scientific field genomic prediction. He called for free universal SNP [single-nucleotide polymorphis] genetic sequencing as part of a shift to genuinely preventive medicine, to be rolled-out across the UK. This approach holds the promise of revolutionising healthcare in ways that give Britain some natural advantages over Europe and America.

Later in the post, Cummings allowed himself to speak more directly to what natural advantages could actually entail. He claimed that a combination of AI-driven machine learning with very large genetic sampling could enable the precise prediction of complex traits such as general intelligence and most diseases.

The two scientists Cummings cited as the primary sources for his vision were educational psychologist Robert Plomin and physicist Steven Hsu.

Plomin, described by Cummings as the worlds leading expert on the subject, is a renowned scientist. But he also has a history of association with the eugenics movement, according to Dr David King, founder of Human Genetics Alert and previously a molecular biologist. (Sir David King, the former chief scientific adviser to the UK Government, has also criticised the genome sequencing goldrush).*

When The Bell Curve a book advocating the genetic inferiority of African Americans was published, Plomin was a key signatory to a statement defending the science behind the book, explained Dr David King in a paper for the non-profit watchdog Human Genetics Alert. The statement carefully avoided explicitly endorsing The Bell Curves racist conclusions (aptly summarised by Francis Wheen as black people are more stupid than white people: always have been, always will be. This is why they have less economic and social success), while failing to repudiate them. Plomins fellow co-signatories included several self-proclaimed scientific racists, Philippe Rushton and Richard Lynn. Plomin has also published papers with the American Eugenics Society and spoken at several meetings of the British Eugenics Society (the latter rebranded itself as the Galton Institute in 1989) both of which advocated racial science.

In December 2013, Plomin was called as an expert witness to the House of Commons Education Select Committee, where he called for the Government to focus on the heritability of educational attainment. Twenty-five minutes into the session, Dominic Raab who as Foreign Secretary and First Secretary has stood in for Boris Johnson during his period of absence due to COVID-19 prompted Plomin to focus more specifically on explaining his views about genetics, intelligence and socio-economic status.

Just two months before Plomins parliamentary testimony, a 237-page dossier by Cummings then a top advisor to Education Secretary Michael Gove was leaked to the press. The paper claimed that genetics plays a bigger role in a childs IQ than teaching and called for giving specialist education as per Eton to the top 2% in IQ. Pete Shanks of the Centre for Genetics and Society described Cummings policy proposal as a blatantly eugenic association of genes with intelligence, intelligence with worth, and worth with the right to rule.

The Cummings dossier which cites Plomin extensively further reveals that, according to Cummings, he had invited Plomin into the DfE [Department for Education] to explain the science of IQ and genetics to officials and ministers.

The Education Select Committees report shows that, at the time of Plomins testimony, the Government was resistant to these views. But, the position appears to have changed since then, with figures such as Cummings, Raab and Gove now at the seat of power under Prime Minister Boris Johnson.

Plomin would go on to work with Steven Hsu, who was involved in a major Chinese genome sequencing project based on thousands of samples from very high-IQ people around the world. The goal was to identify genes that can predict intelligence. Hsu went on to launch his own company, Genomic Prediction. In slide presentations about his work from 2012, Hsu approvingly quoted British eugenicist Ronald Fisher, closing his slides with the following quotation: but such a race will inevitably arise in whatever country first sees the inheritance of mental characters elucidated. Hsus slides, wrote David King, include plans for a eugenic breeding scheme using embryo selection to improve the overall IQ of the population.

Yet, on his blog, Cummings confirmed that Hsu has recently attended a conference in the UK where he presented some of these ideas to UK policy-makers. Among the ideas Hsu presented to Cummings colleagues in Government was that the UK could become the world leader in genomic research by combining population-level genotyping with NHS health records. Hsu further claimed that risk prediction for common diseases was already available to guide early interventions that save lives and money.

Hopefully the NHS and Department for Health will play the Gretzky game, take expert advice from the likes of Plomin and Hsu and take this opportunity to make the UK a world leader in one of the most important frontiers in science, enthused Cummings.

Plomins claim that intelligence is determined primarily by genes contradicts a vast body of scientific literature, and is largely overblown. One of the latest studies debunking Cummings hopes was led by the University of Bristol and published in March. Based on a sample size of 3,500 children, the study found that polygenic scores (which combine information from all genetic material across the entire genome) have limited use for accurately predicting individual educational performance or for personalised education.

The study did not dismiss a role for genes outright, noting genetic scores modestly predictededucational achievement. The problem was that these predictions were less accurate than using standard information known to predicteducational outcomes, such as achievement at younger ages, parents educational attainment or family socio-economic position.

Last November, Hsus Genomic Prediction began touting new report cards to its customers. The cards displayed alleged results of genetic tests containing warnings that embryos might have low intelligence, grow up to be short, or have other conditions such as diabetes. But, according to the MIT Technology Review, the company has struggled both to validate its predictions and to interest fertility centres in them. In the month prior to Hsus grand announcement, the first major study to test the empirical viability of screening embryos, led by statistical geneticist Shai Carmi of the Hebrew University of Jerusalem, concluded that the technology is not plausible.

The lack of scientific substantiation has not stopped Cummings from suggesting a more interventionist vision for the NHS, which could be accused of paving the way for a new form of eugenics. In his February 2019 blog, he wrote: We can imagine everybody in the UK being given valuable information about their health for free,truly preventive medicinewhere we target resources at those most at risk, and early (evenin utero) identification of risks. This passage appears to nod to the core eugenics notion of selective breeding using embryo selection. Cummings even went further to endorse the goal of editing genes to fix problems.

In a further telling but slightly more well-known passage, Cummings characterised the genomics programme as a precursor to more realistic views about IQ and social mobility: It ought to go without saying that turning this idea into a political/government success requires focus on A) the NHS, health, science, NOT getting sidetracked into B) arguments about things like IQ and social mobility. Over time, the educated classes will continue to be dragged to more realistic views on (B) but this will be a complex process entangled with many hysterical episodes. (A) requires ruthless focus.

This passage affirms that Cummings approach is deliberately deceptive. The focus on health and the NHS is revealed as a cover for a longer-term vision to usher in more realistic views about things like IQ and social mobility. The passage also lifts the rock on Cummings weakest point that he fears that public attention on these more realistic views could sidetrack the broader strategy before it reaches fruition.

In the words of Dr David King, Cummings deference to Hsu, who openly advocated eugenics breeding programmes, suggests that the Prime Ministers chief advisor clearly favours this strategy for Britain; of course, this is precisely what all the European countries were trying to achieve in the heyday of eugenics to overcome their imperialist competitors by improving the national stock.

This, it seems, is the essence of Cummings ambition to use the NHS genomics prediction programme as a mechanism to provide Britain natural advantages over Europe and America.

And in this context, it is impossible to ignore the implications of Cummings appointment of Andrew Sabisky to a senior role advising Boris Johnson. When Johnsons spokespeople were asked repeatedly whether the Prime Minister would condemn Sabiskys sympathies for racist eugenics, he repeatedly refused. Sabisky later stepped away from the role.

The COVID-19 pandemic has now provided the Government with the opportunity to double down on its goals of extending genome sequencing across the UK population.

While genomic sequencing of the Coronavirus is undoubtedly an important scientific task to map and understand it, the crisis fits neatly into Cummings call for a ruthless focus on the NHS as a vehicle for Britains genetic enhancement.

On 23 March, when the UK finally instituted a lockdown at least three weeks after being informed that hundreds of thousands of people (and potentially up to a million) people were at risk of death from its previous policy of herd immunity, the Government launched a new scientific research consortium coordinated by Cambridge University along with the Wellcome Sanger Institute, the NHS and Public Health England.

The consortium would gather samples from patients confirmed with COVID-19 and send them to genetic sequencing centres across the country to analyse the whole genetic code of the samples. The project was billed breathlessly as an essential step in being able to control the pandemic and prevent further spread.

Unsurprisingly, it has done no such thing. Instead, six weeks later, the UK has ended up with the highest COVID-19 fatality rate in Europe.

As the death toll approaches the same level of British civilian casualties during the Second World War, the Governments strategy has privileged ambiguous, extortionate high technology solutions, pouring hundreds of millions of pounds into powerful private sector players with no transparency or due process. Meanwhile, traditional, proven, public health strategies such as better border controls, or extensive contact tracing and testing by scaling up local capacity, were inexplicably delayed for months.

On 13 March, the Government launched a new partnership between the NHS, Genomics England, the GenOMICC consortium, and US biotech giant Illumina, to conduct a nationwide human whole genome sequencing study targeting COVID-19 patients in 170 intensive care units.

The Governments new genome sequencing partner, Illumina, has previously produced genetic sequencing systems marketed to police agencies in China to facilitate its genetic profiling of the minority Uyghur population in Xinjang the largest system of discriminatory, ethnically-targeted biometric surveillance using DNA ever created.

It is difficult to avoid the conclusion that Dominic Cummings and his fellow ideologues in Government are hell-bent on pursuing a pseudo-scientific vision that has been years in the making.They are using the COVID-19 crisis to erect a corporate superstate powered by mass surveillance and AI. Their grim ambition is to reach into the very DNA of every British citizen.

Dominic Cummings was contacted for this article, but is yet to reply.

*This article was corrected to remove a confusion between Sir David King, the former government chief scientific adviser, and Dr David King, the molecular biologist who isthefounder and Director of Human Genetics Alert.

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WHITEHALL ANALYTICA THE AI SUPERSTATE: Part 2 Is COVID-19 Fast-Tracking a Eugenics-Inspired Genomics Programme in the NHS? - Byline Times