It has been a very eventful few weeks, especially on the regulatory front. Meanwhile, I have been writing another article with Sarah on the regulation of genetically modified animals, watch this space.

• Spark Therapeutics Luxurna has become the first FDA approved gene therapy that targets a specific gene. It stops the progression of a rare retinal disease.
• First gene-editing in the human body, an individual with the metabolic disease Hunter Syndrome has been injected with a treatment based on Zinc Finger Nucleases and a “correct” copy of the enzyme that his body lacks. 
• For the first time, levels of the protein that causes Huntington’s disease have been lowered, using an antisense drug now licensed by Roche. The drug selectively binds to mRNA made from the mutated HTT gene.
• Mice have successfully been genetically edited to be cured from an inherited form of deafness. The technique is based on CRISPR.
• Biohacker Josiah Zayner made headlines by self-administering CRISPR designed to inhibit myostatin. US law allows for researchers to experiment on themselves. Meanwhile a patient injected himself with an unproven gene therapy. Two companies have said that they will continue to market their DIY CRISPR kits, despite FDA warnings.
• A new version of CRISPR that selectively alters gene expression levels (rather than cleaving DNA). The paper introducing the technique includes encouraging results on mouse models of Muscular Dystrophy and kidney disease. 
• Start-up Inscripta want to democratize gene-editing by making the CRISPR-enzymes freely available. While Cas9 is the enzyme at the core of the IP battle between Berkeley and the Broad, they have made their enzyme, MAD7, publicly available.
• George Church makes the case for a data-driven approach to human germline editing in the NEJM. To the standard slippery slope arguments he retorts: “we often regulate practices on the basis of ethical costs and benefits at specified points along a continuum — for example, speed limits, blood alcohol levels, and age limits. We already embrace many enhancements inherited over multiple generations — generally without consulting future grandchildren — for example, education, homes, and extinction of pathogens through the use of vaccinations.” 
• Craig Venter, he of genome sequencing fame, argues that we should be putting our efforts into continued genomic sequencing and analysis, and that clinical genome editing is not yet ready for primetime. 

• Moderna has started its trial of personalized cancer vaccines.
• The Economist reviews the fledgling enterprises aimed at altering the microbiome to promote health. Seres therapeutics have launched a clinical trial to test their microbe medicine alongside a PD-1 drug.
• Genetic links between lymphoma and auto-immune disease.
• Specific HLA genotypes can lead to better patient outcome on immunotherapies.
• A highly conserved long, non-coding RNA called THOR has been found to be oncogenic.
• A blog post that steams through our historical understanding of cancer, and consequent treatment approaches, which relegates targeted therapies to the history books, and points to atavistic models, in which cancer cells are regarded as having reverted to single-cell organism behaviors, as the current paradigm.

• The first genetic variant protective against aging has been discovered by analysis of an Amish population. Two copies of the variant in SERPINE1 lead to a rare bleeding disorder; one copy leads to longer telomeres and an increased live-span averaging 10%.
• Based on analysis of flies that had been selected based on whether they were extreme short or long sleepers, many candidate loci that can help explain the differences between how long we each need to sleep have been uncovered. These overlap heavily with the usual suspect genes — i.e. genes involved in major pathways: “The involvement of highly pleiotropic pathway genes suggests that sleep duration in natural populations can be influenced by a wide variety of biological processes, which may be why the purpose of sleep has been so elusive.” There was no difference in lifespan between naturally shorter- and longer- sleeping flies.
• Genetic sequencing of a  family who are insensitive to pain has led to the pinpointing of a mutation that researchers hope will eventually help our understanding of chronic pain. 
• The Personal Genome Project, a George Church brainchild whose members contribute their genomic and phenotypic data to the research community, has expanded to China, where it will be the country’s first open science initiative. Says Church,  “I have ridiculously high hopes.”
• An update from Regeneron, who have sequenced >100,000 exomes to date and are headed to a 400-500,000 exomes a year. Their strategy is to partner with groups who have large cohorts of patients with phenotypic data attached, most notably Geisinger Health System and the UK BioBank. They then look for the genetic outliers for ideas of drugs to develop.
• Some heart-warming stories of “extreme parenting”, i.e. the fight that some parents take-up when faced with a diagnosis of an extremely rare condition for a child.
• Three dozen genomes of supercenterians (age >110) have been made publicly available. Supercenterians, unlike centerians, tend to live healthy lives up until the end. This NYT article goes into the tribulations of collecting the samples.
• Genetic variation in the GPCR family of genes (G-protein-coupled receptors), which are targets of about a third of FDA approved therapies, are thought likely to alter drug response in about 3% of individuals.
• A write-up of a conversation at the AMP conference on the legal challenges of variant classification reporting.
• A sketch based on DNA of a suspect in a murder case lead to his arrest and confession.
• An overview of the evidence that there were multiple points at which humans left Africa to populate the rest of the world.
• UK biobank data has been used to demonstrate ways in which humans are still evolving.

• Bacteriophages – viruses that affect bacteria – were formerly believed not to interact with eukaryotic cells, but have now been shown to be absorbed into human cells in the gut, prompting talk of the human phageome, and hypotheses about its role in human health and disease.
• Scientists have added two new functional letters to the genetic code, claiming “The resulting semi-synthetic organism both encodes and retrieves increased information and should serve as a platform for the creation of new life forms and functions.”
• The introduction of a new tool, trim-away, for targeting and destroying specific proteins in cells. The protein trim21 recognizes antibodies, and passes whatever the antibody is tagging to the proteasome – the cell’s destroyer of unwanted proteins. By designing antibodies to target specific proteins, or even variants on these proteins, and delivering them alongside extra trim21, the method can selectively destroy particular proteins.
• Google has released DeepVariant, a deep-learning technique for variant calling that it claims produces more accurate results than previously existing software, by transforming the problem into one of image analysis.
• Luna, a blockchain based genomic start-up, have raised $2m in seed-funding. They will reward those who contribute their DNA for research, and provide increased security, with their own blockchain based coin.

• A review of protections against genetic discrimination offered by GINA argues that protections should be strengthened. Currently, a Californian woman with a positive BRCA result could legally be denied a mortgage on the basis of decreased life expectancy.
• New FDA guidelines to implement gene-therapies faster.
• On the 14th Nov the The US Senate Committee on Health, Education, Labor, and Pensions held a hearing on CRISPR genome editing. I have yet to listen to the hearing itself, but this write-up makes it comes across as somewhat self-congratulatory in terms of regulatory approach. The ranking senator apparently called on scientific consensus on the ethical questions, which are not words I expected to ever come across strung together in that order.
• On regulation of somatic panel tests, GenomeWeb summarizes nicely: “The agency authorized Memorial Sloan Kettering Cancer Center’s MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets) through the de novo premarket review pathway as a Class II, moderate-risk device, and simultaneously made the New York State Department of Health a third-party reviewer of IVDs, including similar tumor profiling assays. Subsequently, other labs can apply to the FDA for 510(k) clearance — a less onerous path than premarket approval — for their tumor profiling NGS panels. Or, if the test already has approval through the NYSDOH, sponsors can submit that application to the FDA and ask the state regulator to forward its review documents and recommendations.”
• Meanwhile the FDA approved FoundationOne, and the CMS simultaneously agreed to pay for it.
• A perspective in the NEJM that a proposed Act will worsen the regulatory landscape in health. The authors argue that the Regulatory Accountability Act, a version of which will so go before the Senate, will actually stifle innovation because regulation will not be able to keep up with technology, and it will be harder to retire old regulation.
• The FDA has issued a flurry of new proposed guidance, two on running of clinical trials for targeted therapies (one on the design of assays for trials here, one on appropriately exempted diagnostic tests here), and one on clinical and patient decision support software here.
• The NIH has lifted a ban on gain of function viral research. The ban was instituted in 2014 when based on research that developed a virus that was more easily transmitted.
• The Chinese FDA has approved a self-sampling based test for HPV from BGI. 
• A group of gene-drive researchers have put together guiding principles for the use of gene drives, as part of a coordinated response to the NASEM report that concluded that gene drives were not ready for deployment, based on currently available evidence.
• A call for more DNA collection of those charged with crimes, based on data from Denmark, where they massively increased their DNA collection rate: “Our results thereby show that policies that increase the identification of criminal offenders are an effective tool to reduce crime and increase public safety,”