National Academies on the Call for Moratorium on and International Governance of Heritable Gene Editing

Statement on Call for Moratorium on and International Governance Framework for Clinical Uses of Heritable Genome Editing

“A commentary published in Nature calls for a moratorium on clinical uses of heritable human genome editing and the establishment of an international governance framework. (We responded to the commentary with a joint letter, which is an abbreviated version of this statement.) The call comes following claims by a scientist in China to have edited the genes of early embryos, in treatments that resulted in the birth of twins. The scientist’s work – revealed at the Second International Summit on Human Genome Editing in Hong Kong, jointly organized by our Academies, was condemned by the summit organizers and by much of the wider scientific community.”

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Heavyweights call for moratorium on heritable genome editing

Adopt a moratorium on heritable genome editing

Eric Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg and specialists from seven countries call for an international governance framework.

We call for a global moratorium on all clinical uses of human germline editing — that is, changing heritable DNA (in sperm, eggs or embryos) to make genetically modified children.

By ‘global moratorium’, we do not mean a permanent ban. Rather, we call for the establishment of an international framework in which nations, while retaining the right to make their own decisions, voluntarily commit to not approve any use of clinical germline editing unless certain conditions are met.

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Population-specific structural variation

Genome maps across 26 human populations reveal population-specific patterns of structural variation

Abstract—Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome.

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A discussion of the limitations of a single, static reference genome

Buffalo gave us spicy wings and the ‘book of life.’ Here’s why that’s undermining personalized medicine

“The human reference genome, largely completed in 2001, has achieved near-mythic status. It is “the book of life,” the “operating manual for Homo sapiens.” But the reference genome falls short in ways that have become embarrassing, misleading, and, in the worst cases, emblematic of the white European dominance of science — shortcomings that are threatening the dream of genetically based personalized medicine.“

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Disease risk estimates need more samples from more populations (Genome Biology)

Genetic disease risks can be misestimated across global populations

Michelle S. Kim, Kane P. Patel, Andrew K. Teng, Ali J. Berens, and Joseph Lachance

Genome Biology (Research article)

Accurate assessment of health disparities requires unbiased knowledge of genetic risks in different populations. Unfortunately, most genome-wide association studies use genotyping arrays and European samples. Here, we integrate whole genome sequence data from global populations, results from thousands of genome-wide association studies (GWAS), and extensive computer simulations to identify how genetic disease risks can be misestimated. In contrast to null expectations, we find that risk allele frequencies at known disease loci are significantly different for African populations compared to other continents. 

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Alzheimers insights from the desk of the NIH Director, Dr. Francis Collins

Largest-Ever Alzheimer’s Gene Study Brings New Answers

Predicting whether someone will get Alzheimer’s disease (AD) late in life, and how to use that information for prevention, has been an intense focus of biomedical research. The goal of this work is to learn not only about the genes involved in AD, but how they work together and with other complex biological, environmental, and lifestyle factors to drive this devastating neurological disease.

It’s good news to be able to report that an international team of researchers, partly funded by NIH, has made more progress in explaining the genetic component of AD. Their analysis, involving data from more than 35,000 individuals with late-onset AD, has identified variants in five new genes that put people at greater risk of AD [1]. It also points to molecular pathways involved in AD as possible avenues for prevention, and offers further confirmation of 20 other genes that had been implicated previously in AD.

The results of this largest-ever genomic study of AD suggests key roles for genes involved in the processing of beta-amyloid peptides, which form plaques in the brain recognized as an important early indicator of AD. They also offer the first evidence for a genetic link to proteins that bind tau, the protein responsible for telltale tangles in the AD brain that track closely with a person’s cognitive decline.

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50,000 Human Exomes at the UK Biobank

New genetic data on 50,000 UK Biobank participants made available to the global health research community

A vast tranche of new UK Biobank genetic data becomes available to health researchers today, offering an unprecedented resource to enhance understanding of human biology and aid in therapeutic discovery.

The exome sequence data of 50,000 UK Biobank participants were generated at the Regeneron Genetics Center through a collaboration between UK Biobank, Regeneron (US) and GSK (UK) and are linked to detailed health records, imaging and other health-related data. Regeneron is also leading a consortium of biopharma companies (including Abbvie, Alnylam, AstraZeneca, Bristol-Myers Squibb, Biogen, Pfizer and Takeda) to complete exome sequencing of the remaining 450,000 UK Biobank participants by 2020. In addition, GSK has committed a £40 million investment to initiatives, such as UK Biobank, that harness advances in genetic research in the development of new medicines

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EU pathway for improve rare disease identification and treatment

New EU platform to support better rare disease diagnosis and treatment

The European Commission is launching a new online knowledge-sharing platform to support better diagnosis and treatment for more than 30 million Europeans living with a rare disease.

Currently a vast amount of data on patients with specific conditions is scattered across Europe in about 600 'registries' – databases that hold information on patients with specific conditions. Data is not collected EU-wide and there are no shared standards to analyse the information that is available on rare diseases. The new European Platform on Rare Diseases Registration will bring this data together supporting the quality research that can enhance diagnosis and treatment outcomes - helping to improve the lives of patients and their families.

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Let's now worry about designer babies ...

The Dawn of Intelligent Designer Babies

While selecting or editing embryos in favour of certain attributes may seem like a phenomenon of the distant future, the company Genomic Prediction in the United States has recently announced their advanced technology that would allow parents to screen for several complex traits, most controversially being low intelligence. This process would give the option of excluding embryos during in vitro fertilisation (IVF) that have a high risk of having “mental disability,” defined as an IQ of 25 points below average. While Genomic Prediction explicitly states that this will not be used to select for embryos with the potential for abnormally high intelligence, co-founder Stephen Hsu claims it is entirely feasible and states “I think people are going to demand that. If we don’t do it, some other company will.”

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Centers for Medicare & Medicaid Services cancer sequencing dust-up

CMS Acknowledges Stakeholder Concerns Over Decision Not to Cover Germline NGS in Early Cancer Patients

NEW YORK (GenomeWeb) – The Centers for Medicare & Medicaid Services issued a notice this week acknowledging the confusion over its coverage policy for germline next-generation sequencing for cancer patients.

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More than four possible bases, more coverage

Scientists Have Created Synthetic DNA with 4 Extra Letters

A couple billion years ago, four molecules danced into the elegant double-helix structure of DNA, which provides the codes for life on our planet. But were these four players really fundamental to the appearance of life — or could others have also given rise to our genetic code?

A new study, published today (Feb. 20) in the journal Science, supports the latter proposition: Scientists have recently molded a new kind of DNA into its elegant double-helix structure and found it had properties that could support life.

But if natural DNA is a short story, this synthetic DNA is a Tolstoy novel.

The researchers crafted the synthetic DNA using four additional molecules, so that the resulting product had a code made up from eight letters rather than four. 

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Increased CRISPR specificity by limiting expression

Scientists sharpen their molecular scissors and expand the gene editing toolbox

Wake Forest Institute for Regenerative Medicine (WFIRM) scientists have figured out a better way to deliver a DNA editing tool to shorten the presence of the editor proteins in the cells in what they describe as a "hit and run" approach.

CRISPR (clustered regularly interspaced short palindromic repeats) technology is used to alter DNA sequences and modify gene function. CRISPR/Cas9 is an enzyme that is used like a pair of scissors to cut two strands of DNA at a specific location to add, remove or repair bits of DNA. But CRISPR/Cas9 is not 100 percent accurate and could potentially cut unexpected locations, causing unwanted results.

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Smart stats make use of large-scale health insurance claims

Repurposing large health insurance claims data to estimate genetic and environmental contributions in 560 phenotypes

We analysed a large health insurance dataset to assess the genetic and environmental contributions of 560 disease-related phenotypes in 56,396 twin pairs and 724,513 sibling pairs out of 44,859,462 individuals that live in the United States. We estimated the contribution of environmental risk factors (socioeconomic status (SES), air pollution and climate) in each phenotype. Mean heritability (h2 = 0.311) and shared environmental variance (c2 = 0.088) were higher than variance attributed to specific environmental factors such as zip-code-level SES (varSES = 0.002), daily air quality (varAQI = 0.0004), and average temperature (vartemp = 0.001) overall, as well as for individual phenotypes. We found significant heritability and shared environment for a number of comorbidities (h2 = 0.433, c2 = 0.241) and average monthly cost (h2 = 0.290, c2 = 0.302). All results are available using our Claims Analysis of Twin Correlation and Heritability (CaTCH) web application.

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Extended genetic alphabet covered in New York Times

DNA Gets a New — and Bigger — Genetic Alphabet

DNA is spelled out with four letters, or bases. Researchers have now built a system with eight. It may hold clues to the potential for life elsewhere in the universe and could also expand our capacity to store digital data on Earth.

In 1985, the chemist Steven A. Benner sat down with some colleagues and a notebook and sketched out a way to expand the alphabet of DNA. He has been trying to make those sketches real ever since.

On Thursday, Dr. Benner and a team of scientists reported success: in a paper, published in Science, they said they have in effect doubled the genetic alphabet.

Natural DNA is spelled out with four different letters known as bases — A, C, G and T. Dr. Benner and his colleagues have built DNA with eight bases — four natural, and four unnatural. They named their new system Hachimoji DNA (hachi is Japanese for eight, moji for letter).

Crafting the four new bases that don't exist in nature was a chemical tour-de-force. They fit neatly into DNA’s double helix, and enzymes can read them as easily as natural bases, in order to make molecules.

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CRISPR Gene Editing advances

Gene Editing is trickier THAN expected—BUT fixes are in sight

Of all the big, world-remaking bets on the genome-editing tool known as Crispr, perhaps none is more tantalizing than its potential to edit some of humanity’s worst diseases right out of the history books. Just this week, Crispr Therapeutics announced it had begun treating patients with an inherited blood disorder called beta thalassemia, in the Western drug industry’s first test of the technology for genetic disease. But despite the progress, there remain a host of unknowns standing in the way of Crispr-based medicines going mainstream, chief among them safety.

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World Health Organization might make some human genome editing rules

Human genome editing is here – now we have to decide who is in charge

The World Health Organization (WHO) will convene a meeting this month to develop global standards of governance for human genome editing. This is a welcome move. Although the committee has no powers to enforce compliance – it is still a matter for individual nations to decide on regulations, with China reportedly updating its rules earlier this week – the WHO committee’s recommendations will be influential and far-reaching in their ambition. But I hope committee members will bear a few points in mind in their discussions.

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Synthetic DNA is a new technology and probably needs some new rules

Opinion: Ethical Boundaries Needed on the Uses of Synthetic DNA

A newly expanded genetic alphabet that includes four synthetic nucleotides highlights the need for strict boundaries on their use.

A study published last week expands the redesign of the 4-billion-year-old genetic code from a four-nucleotide base-pair alphabet to an eight-base-pair alphabet by incorporating artificial nucleotides. The scientists, led by Steven Benner of the Foundation for Applied Molecular Evolution and Firebird Biomolecular Sciences in Florida, have also identified a bacteriophage RNA polymerase variant that transcribes the synthetic DNA into synthetic RNA.  

Previously, a scientific team led by Floyd Romesberg at The Scripps Research Institute used its own synthetic base pairs to create bacteria that replicate the artificial DNA, translate the DNA into mRNA, and create new types of amino acids. 

These are technologically impressive accomplishments and the translational applications of these discoveries could be revolutionary.

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A European take on CRISPR corn

Boosting corn yields with CRISPR-carrying pollen

Scientists have developed a single-step gene editing process that can increase corn yields.
The new technique uses pollen to transfer the components of CRISPR-Cas9 into another plant allowing them to produce gene edited corn, a process previously hindered by the thick cell walls of many plants, such as corn and wheat. Results of the first set of experiments were published on 4 March in Nature Biotechnology.

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What will human cloning be like, when we eventually start doing it...

#Science #Biology #Medicine #HumanCloning #Future

It had looked impossible, but, in the end it was surprisingly easy. So, though few knew of their creation at the time, the first human clones were born in 2020 in Taiwan. Now, as those clones celebrate their 30th C-days, it seems a good moment to review the history of cloning…

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CRISPR off-target errors

A CRISPR spin-off causes unintended typos in DNA

Even the best editor sometimes introduces typos. That’s true whether the editor is human or a version of the much-heralded gene-editing tool CRISPR.

One type of CRISPR gene editor that changes individual DNA bases, rather than cutting DNA, introduces more unwanted mutations than expected in mouse embryos and rice plants, researchers report. Those mistakes occurred in places where the tool wasn’t supposed to make changes. Another tested base editor, however, didn’t make the undesirable edits. The results were described in two studies published online February 28 in Science.

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