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Sjon shared this story from WIRED » Security.

Flight AND fight.

The post So, Dutch Cops Are Teaching Majestic Eagles to Hunt Drones appeared first on WIRED.

IIlumina’s MiniSeq Sequencing System

Illumina announced MiniSeq, a new benchtop sequencing system, at this year’s JPM. With MiniSeq, Illumina hopes to offer NGS workflow solution for every lab. MiniSeq is priced at $49,500 USD, to make it easy for any laboratory to adopt NGS. The MiniSeq System is expected to be available early in the first quarter of 2016.

MiniSeq can sequence up to 2x 150 bp paired reads with the throughput of 4-50 Million reads and about 6.6 Gb to 7.5 Gb data with high-output kit. Check the MiniSeq system specification pdf for more information.

MiniSeq Specifications for Different Applications

The press release announcing the MiniSeq, said

The new MiniSeq System makes Illumina’s trusted sequencing technology accessible to all laboratories interested in performing targeted sequencing. With push-button operation, the flexible benchtop sequencer enables a broad range of DNA and RNA sequencing applications, from examining single genes to entire pathways, in a single run. Priced at $49,500 USD, and cost-efficient to run, the affordable MiniSeq System allows virtually any laboratory to adopt NGS, regardless of sample volume.

The research-use only MiniSeq System is designed and being commercialized as part of a complete sequencing solution that enables both experienced and new-to-NGS researchers to get results quickly with an easy-to-use library-to-results workflow and onboard data analysis for numerous assays. The sequencer is also able to stream sequencing data to BaseSpace®, Illumina’s cloud and onsite genomics computing environment. Compatible with a full suite of Illumina library preparation solutions, and end-to-end support from Illumina scientists and engineers, the MiniSeq System is an ideal NGS workflow solution for many applications commonly performed by molecular biologists, translational researchers in oncology, and molecular pathologists.

Announcing the MiniSeq benchtop sequencing system #JPM16

— Illumina (@illumina) January 11, 2016

MiniSeq is an ideal NGS workflow solution for molecular biology, translational oncology, molecular pathology research #JPM16

— Illumina (@illumina) January 11, 2016

MiniSeq is an ideal NGS workflow solution for molecular biology, translational oncology, molecular pathology research #JPM16

— Illumina (@illumina) January 11, 2016

In addition to the MiniSeq, Illumina offered hints about their new sequencing technology, Project Firefly, Sequencing-by-synthesis chemistry on a semiconductor chip, with data similar to HiSeq X. Illumina expects to commercialize Project Firefly in the second half of 2017.

Illumina also previewed a new sequencing system designed to democratize NGS and truly enable the adoption of genomics worldwide. The highly-reliable, easy-to-use NGS platform will offer customers a low capital cost and plug and play installation. The most integrated sequencer ever developed, the system will take users from purified DNA to answers, making it the ideal tool for virtually any laboratory. The stackable two module system will minimize hands-on time for both library preparation and sequencing. Leveraging Illumina digital fluidics technology, the first module will make library preparation simple and efficient preparing eight normalized samples in parallel on a library preparation cartridge. A separate cartridge for sequencing, loaded into the second module, will deploy a one channel version of Illumina’s sequencing-by-synthesis chemistry on a semiconductor chip. Sequencing data will seamlessly move to BaseSpace for analysis.

The new system will be superior to competing semiconductor-based sequencing systems with a raw error rate of less than one percent, data quality comparable to that of a HiSeq XTM Sequencing System. With output of approximately 1.2G per run, the platform will be ideal for numerous markets including academic research, oncology, infectious disease, inherited disease, and reproductive health.

Illumina expects to commercialize this system in the second half of 2017, priced at less than $30,000 USD for both modules. For customers running eight samples at once, the company projects per-sample consumable pricing near $100.

$ILMN to launch new hand held sequencing platform – Project Firefly – based on CMOS tech. Output >1G, accuracy = HiSeqX @ $30K #jpm16

— Gautam Kollu (@gautamkollu) January 11, 2016

Aging happens to all of us, and is generally thought of as a natural part of life. It would seem silly to call such a thing a “disease.”

On the other hand, scientists are increasingly learning that aging and biological age are two different things, and that the former is a key risk factor for conditions such as heart disease, cancer, arthritis, Alzheimer’s disease, and many more. In that light, aging itself might be seen as something treatable, the way you would treat high blood pressure or a vitamin deficiency.

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Cancer treatment is like an arms race. After a tumor evolves resistance to one drug, doctors switch to another therapeutic weapon — and on and on, until the tumor is vanquished or the drug cupboard is bare.

But a case study published Wednesday in the New England Journal of Medicine suggests this steady battle march can sometimes swing around on itself.

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Can you ice your way to a slimmer body? New products and procedures keep popping up, promising to help you do just that. Intuitively, the idea makes sense: The colder you get, the more your body has to work to heat itself up, and that extra effort should burn calories.

A study out this month boosted the theory with a tantalizing hint that cold could help spur weight loss by changing the microbiome (at least in mice).

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Sjon shared this story .

As it turns out, I did find a "million-dollar bug" in Instagram (specifically I gained access to a lot of data including SSL certs, source code, photos, etc), but that's really only the start to the story.

Related Articles

Construction and optimization of an efficient amplification method of a random ssDNA library by asymmetric emulsion PCR.

Biotechnol Appl Biochem. 2015 Dec 16;:

Authors: Shao K, Shi X, Zhu X, Cui L, Shao Q, Ma D

Abstract
Construction of a random ssDNA sublibrary is an important step of the aptamer screening process. The available construction methods include asymmetric PCR, biotin-streptavidin separation, and lambda exonuclease digestions, in which PCR amplification is a key step. The main drawback of PCR amplification is overamplification increasing nonspecific hybridization among different products and by-products, which may cause the loss of potential high-quality aptamers, inefficient screening, and even screening failure. Cycle number optimization in PCR amplification is the main way to avoid overamplification but does not fundamentally eliminate the nonspecific hybridization, and the decreased cycle number may lead to insufficient product amounts. Here, we developed a new method, "asymmetric emulsion PCR," which could overcome the shortcomings of conventional PCR. In asymmetric emulsion PCR, different templates were separated by emulsion particles, allowing single-molecule PCR, in which each template was separately amplified, and the nonspecific hybridization was avoided. Overamplification or formation of by-products was not observed. The method is so simple that direct amplification of 40 or more cycles can provide a high-quality ssDNA library. Therefore, the asymmetric emulsion PCR would improve the screening efficiency of systematic evolution of ligands by exponential enrichment.

PMID: 26671010 [PubMed - as supplied by publisher]

For the busy scientist, a Smartphone is more than just a Facebook and Instagram viewer. In the past few years, apps have been developed that can also allow you to use your phone or tablet to design PCR and qPCR experiments on the go. This technology evolves rapidly though. Today, I’ll describe my experiences with two PCR apps that have appeared just within the past year. Both are free (my favorite!) and compatible with iPhone, iPad and iPad Touch, while the second one works with Android systems as well. So without further ado, let me tell you about them.

PCR Essentials

From Life Technologies this PCR app requires iOS 7.0 or later. This app may appear simple, but it packs a punch. PCR Essentials will help you find PCR products for purchase (plasticware, polymerases, cDNA kits, etc.) and calculate mastermix reaction components. But the most amazing thing to me is that with this app you can connect remotely with your ProFlex PCR instrument, if you have one. Can you imagine stepping out of the lab for lunch, but still being able to check on the progress of your PCR reaction? It looks like this app will let you do this. Full disclosure: I don’t have a ProFlex PCR System, so I couldn’t test this particular feature myself. If you have one, please let me know about it in the comment section. I’d love to hear about your experience.

Figure 1: PCR Essential’s Homepage. Don’t let the simplicity fool you this is a comprehensive app.

PCR Essentials also has PCR-related videos that you can watch while you wait for your reaction to complete – ranging from “Competent Cell Transformation” to cheesy PCR-themed musical cartoons. The strength of this app is that you can access a lot of different PCR resources all within this single app, instead of using separate PCR apps for each feature. While the homepage of PCR Essentials not too fancy-looking, see Figure 1, it is very useful.

Real-Time PCR

This is another free app in the Life Technologies PCR series. It requires an operating system of iOS 6.0 or later. Also, as of June 2015, there is now an Android version available. Real-Time PCR comes with a complete PCR handbook that covers a wide variety of topics including Experimental Design, Plate Preparation, Data Analysis and Troubleshooting. These topics are all well-organized too, making referencing easy and making this app a great on-the-go resource for all the students in your lab.

Figure 2: Real-Time PCR’s Homepage features a Handbook section and Publications section for easy on-the-go referencing.

Especially notable is Real-Time PCR ‘s handy troubleshooting guide. This guide covers common problems such as abnormal amplification, poor PCR efficiency and genotyping issues. Good for both the summer undergrad and the experienced postdoc. This app also has several technical videos that cover the basics of PCR, digital PCR, gene expression and instrumentation. To round out its functionality, there is also the obligatory reaction mix calculator, a bookmark option, and a form to contact Life Technologies technical support. As with PCR Essentials (and as you can see in this screenshot of the homepage) this app covers a lot of territory that used to require multiple apps.

Other PCR Apps

In addition to these two major (read: comprehensive) PCR apps, there are a few others I would be remiss to not mention including Life Technologies Digital PCR in 3D. This is not a brand new app (2013), but has instructional videos on digital PCR, Chip Technology, Quantification and Rare Target Detection, an interactive demo, as well as a link to the Life Technologies user community forum. GeneLink (iOS 3.2 or later) is an app that dates back to 2012, but may be a good option for those with older devices. It has reaction mix calculators, a reference section with information on basic nucleic acid biology, a list of available products and a company contact page.

This is not meant to be an exhaustive list of smartphone PCR apps, but rather some of the newer and most helpful ones. For past articles on oldie but goodie PCR-related apps see Ellen Moran’s article “Apps That Bring PCR to Your Mobile Device” and Nick Oswald’s article “10 More iPhone/ipad Apps for Bioscientists”.

If these new PCR apps are any prediction for the future, all PCR instruments will be controllable by smartphone. Remote lab management seems to be the way of the future with new applications being developed all the time. But meanwhile, if your supervisor comes into the lab and happens to catch you staring at the “Words With Friends” game on your smartphone, you could always try to brush it off as a new primer designing tool. Good luck!

The post Smartphone PCR Apps for PCR-On-The-Go appeared first on Bitesize Bio.

WASHINGTON — The International Summit on Human Gene Editing is wrapping up on Thursday after three days of formal talks, panel discussions, and audience questions on altering the DNA of sperm, eggs, or early embryos — the human “germline” — so that the repairs are passed down to any future children. The prospect of altering human heredity in this way is controversial, to say the least, but it has become a real possibility because of the development of the CRISPR-cas9 gene-editing system.

The meeting has had its share of Tweetable moments: One participant said China will spend $400 million over the next five years on genome-editing research. George Church of Harvard Medical School said the dread prospect of “genetic enhancement” of embryos (a.k.a. designer babies) might come creeping through the back door — as patients with muscle-wasting diseases get their in vitro fertilization embryos engineered to prevent that disease in their children, and then other prospective parents will want that strong-muscle gene so that their embryo can grow into an Olympian. And it became clear that genome editing will likely reopen the bitter debate over embryo creation and destruction.

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At the American Society of Human Genetics meeting in October, CRISPR-Cas9 inventors Jennifer Doudna and Emmanuelle Charpentier accepted the Gruber Genetics Prize, then stopped by the press room. For me, this was a little like sitting down with Bono and Bruce Springsteen, but the women were wonderfully down-to-earth, and a little stunned at all the attention since they published their key paper in 2012 on the technique that is speeding gene editing and making genome editing possible.

This week an International Summit on Human Gene Editing held in Washington DC discussed the potential promises and pitfalls of gene editing technology. Here is an excellent review. For those of us who were around at the debut of modern biotechnology in the 1970s, it’s déjà vu all over again, and I hope the outcome will be the same. Although concern over recombinant DNA technology back then began with alarm, it basically ended with not triple-headed purple monsters, as my then-grad-school advisor dubbed the concern, but with a new and more targeted source of drugs, beginning with human insulin.

Below are selected comments from Drs. Doudna (a Howard Hughes Medical Institute Investigator and professor of molecular and cell biology and chemistry at the University of California, Berkeley) and Charpentier (director of the new Max Planck Institute of Infection Biology) from their Gruber award acceptance speeches and visit to the press room in October. I’ll cover here what I didn’t a few weeks ago (here and in Medscape).

RL: Why is CRISPR-Cas9 taking off right now?

Jennifer Doudna (JD): I watched a video by Bill Gates and Steve Wozniac from the beginning of the personal computer age 25 years ago. When they were asked when they realized the PC was going to take off, they said it was serendipitous, because society was at a point where people were ready and eager to adopt that technology. That’s a very interesting parallel to CRISPR-Cas9.

We had the first bacterial genome in 1995, that’s 20 years ago. And with all the genome-wide association studies and human genome sequencing since 2000, we’ve built up an appreciation for the kinds of mutations that cause disease and the desire to be able to manipulate genes beyond systems like yeast and worms. We’re seeing the convergence of those technologies with an efficient and easy way to manipulate genes.

If this had happened 10 years ago we might have seen a different trajectory. In PubMed (for the 2012 paper) it’s exponential: 120 citations the first year, 400 in 2013, 600 in 2014, and more than 1200 as of October 2015. There was a pent-up need for the technology to manipulate genomes to be easy, and that’s what we’re seeing now.

RL: How did your research paths converge?

Emmanuelle Charpentier (EC): I was trying to understand how bacteria cause infectious diseases, from the pathogen and the human sides, particularly Streptococcus pyogenes. It causes necrotizing fascilitis, toxic shock syndrome, myositis, tonsillitis, pharyngitis, impetigo, cellulitis, scarlet fever, rheumatic fever, reactive arthritis, and rheumatic fever. I was also interested in infection of bacteria by invading genomes. Mobile genetic elements (bacteriophage) attack a bacterial host, and the host has a defense against the invaders that is considered the innate immune system of bacteria.

JD: Precision-editing a genome isn’t a new idea, it’s been around for decades. In the 1980s, as a grad student, I was working on double strand DNA break repair. The field of genetics has long appreciated that the ability to make changes in DNA would be an incredibly useful tool. The 2007 Nobel Prize in Physiology or Medicine (to Mario Capecchi, Martin Evans, and Oliver Smithies) was for harnessing homologous recombination, one of two DNA repair pathways activated by double strand breaks, to create the knockout mice that have since served as models for many human genetic diseases.

Our own journey was going from the basic science from Emmanuelle through our realization that we had come across a pathway in bacteria that could be harnessed as a powerful genome engineering technique. I started with a small NSF grant 10 years ago, before anyone thought this would be useful for anything.

EC: I started to work on this in 2006, using bioinformatics, then more seriously in 2009, with this paper in 2011.

RL: How Does CRISPR-Cas9 Work? The short version, that is.

EC: The enzyme Cas9, an endonuclease, is programmed with a guide RNA to target and cleave a specific DNA sequence at two strands. The manipulator just needs to engineer the guide RNA according to the sequence of the gene to be modified.

JD: Bacteria defend against viral infection by acquiring little bits of DNA from viruses into their genomes, making RNA copies of viral sequences, and incorporating them into one or more proteins used to target the viral DNA. Then the RNA-protein complex finds double-stranded regions, unwinds them, and positions itself so two active sites can cut the double-stranded DNA at a precise, targeted sequence. Cells recognize double strand breaks and repair them using two pathways that add new sequence or heal the old. It is a remarkable molecular machine that can search through large slots of DNA to find a particular sequence.

EC: The idea was relatively simple: genome editing with sequence-specific nucleases inducing a double strand DNA break at a specific site. The RNA-programmable CRISPR-Cas9 allows precise surgery in the cells of many organisms, including mice, plants, monkeys, and humans.

JD: Bacteria use CRISPR-Cas9 to cut a viral DNA sequence, but scientists harness it to make double strand breaks where we might like to introduce a small change in the genome.

(Dr. Doudna explains the nuances of CRISPR-Cas9 in this video.)

RL: The ease of deploying CRISPR-Cas9 has raised concerns that it will be used to alter the genome of a fertilized ovum. In April, researchers from Sun Yat-sen University published that they’ve already done this. Why the concern over germline modification?

JD: When I saw the publication in early 2014 of germline editing in monkeys, it came home to me that there’s no reason to think it couldn’t also be used in humans. Why not? That raises ethical questions as well as considerations about the utility for applications where it’s easy to employ, yet we as scientists should take a step back and say “should be go there?” Those thoughts are what launched me on the path I’m currently on in bringing colleagues on board to discuss the bioethics openly.

Doing somatic (body) cell editing in adults has inherently more immediate applications because we don’t have to think about the ethics of passing on heritable mutations. On the other hand, in some ways it will be harder to do because we have to deliver to adult tissues. Ironically, germline application is a lot easier to deliver. If we know there is an inborn genetic error, it could be more efficient and safer to correct it at an early stage of embryonic development than if we wait to do it in an adult patient.

RL: What are some non-medical uses of gene and genome editing?

JD: Gene drive technology is an approach using CRISPR-Cas9 that could lead to elimination of species by changing organisms in ways that make them sterile, such as mosquitoes. It’s not science fiction anymore, it’s here right now. (A recent paper details using CRISPR-Cas9 to create malaria-resistant Aedes aegypti mosquitoes.)

A researcher is using CRISPR-Cas9 to study the genetic changes in going from a mouse to a jerboa, a hopping desert rodent. It has huge hind legs and is bipedal. A jerboa is genetically very similar to a mouse, but clearly different in phenotype. Until using CRISPR-Cas9 to interrogate the genome of this organism, it was completely intractable genetically. We can now introduce changes to that organism and possibly reconstruct evolution.

Third-graders are using CRISPR-Cas9 to change a DNA sequence in yeast. A colorometric assay manipulates yeast that turn blue. It is a genome engineering change that is so simple to use. For $65 you can order reagents from AddGene, the “nonprofit plasmid repository,” and in a week or two have genome-modified cells. It’s phenomenal. (I was unable to locate a kit targeted especially for students although I suspect the folks at Carolina Biological Supply are onto it.)

EC: There’s an interesting debate about using CRISPR-Cas9 on plants to create GMOs. That’s very restrictive in Europe. There they may not accept CRISPR-Cas9 in any plant, because they may not consider plants that have deleted genes to be non-GMOs. Decisions will be made in Europe by the end of the year.

JD: The US Department of Agriculture ruled that if a genetic manipulation results in a knockout, it’s not a GMO.

(HISTORICAL ASIDE FROM RL: Those of a certain age will recall the famous Frostban “ice-minus” bacteria, common Pseudomonas syringae with a gene removed that, when put on strawberry plants, enables them to survive frost. Environmentalists successfully blocked the first field tests, although the manipulated bacteria merely mimicked a naturally-occurring mutation. An article in The Scientist chronicled the hysteria with compelling anti-science quotes. My favorite: a plea that the genetically deficient bacteria would cause “more death and destruction than all the wars we have ever fought.” But of course designing babies is different from helping strawberries.)

JD: These concerns mean there’s a real need to discuss the science. I met a researcher who’s working in South Korea on bananas, and I’m from Hawaii and I know banana farmers. Bananas are genetically very similar to each other and that makes them highly susceptible to disease. Currently a fungus is wiping out bananas. In the end it may come down to a choice, not whether we want GMO or non-GMO bananas, but whether we want bananas or not? If we want bananas, people might have to accept a fungal resistance gene that has been introduced.

All of these areas are exciting and require serious consideration before forging ahead.

RL: I hope Tabitha Powledge, at her terrific PLOS blog “On Science Blogs,” will follow the media interpretation of this week’s conference on gene editing in her post tomorrow.

(Thanks to Ernesto del Aguila III of NHGRI for the CRISPR-Cas9 graphic.)

Oxford Nanopore’s (ONT) MinION is probably the next-generation sequencer users are most excited about getting working in their own labs. ONT announced the system back in 2012 at Advances in Genome Biology and Technology, the biggest sequencing technology conference, to a packed auditorium. I was in the audience and was as stunned as anyone else that this technology seemed close to a reality, before Clive Brown spoke people would have said that a USB sequencer not much bigger than a memory stick which could sequence genomes in 50kb+ read-lengths was impossible “’Star Trek’ technology!”

In 2014, ONT opened the MinION Access Program (MAP) to give users a chance to see what they could do with the technology. The MAP has been a huge success with over 1000 MinION’s being used across the globe (including two in my lab), but anyone following the technology outside of the MAP would have heard lots of noise in discussions. Much of the real talking is taking place in the MAP community which is not open access; the first publication was overly critical of what was a very early technology release, but subsequent publications have show that is it possible to sequence and assemble whole genomes, e.g., E. coli and Yeast.

Nanopore sequencing can deliver and I got an update from multiple users at the UK Genome Science conference. Library prep methods are pretty standard: DNA, frag, end repair, A-tail, adapter ligation. Sequencing accuracy is improving: at least 85% raw base accuracy, but with 2D reads or consensus sequencing you can achieve 99.4%.

WIMP Workflow

The WIMP (What’s In My Pot) workflow. This very rapidly aligns sequence reads to a “genome database” to detect and quantify different species of bacteria, it is possible to perform this analysis in real-time and discard fragments that you do not want to sequence any more – this offers a revolutionary way to sequence almost exactly what you want and no more. Dan Turner’s group at ONT is developing an automoated library prep system called Voltrax and have been using iChips to grow normally unculturable cells for genome analysis.

minoTaur

minoTaur is an analysis package that lets you manage, analyze and manipulate reads generated by the Oxford Nanopore MinION technology. The tools allow a user to specify a coverage depth for a specific barcoded sample, and even a specific region of the genome, to minimize sequencing coverage variation across samples in a pool; you can even get the run to autofinish once enough data has been collected, and Tweet when a specific variant is detected! The package was used to normalize reads in the Ebola sequencing project to minimize the amount of data being transferred across flaky WiFi and satellite phone technology.

The MinION was used to sequence Ebola in real-time and impact the spread of this devastating disease. Everything needed to sequence Ebola in the field went on a plane in a few cases, with USB temperature data loggers to verify if reagents were likely to be OK after transit. Within 48 hours of arrival, the first sequences were being uploaded to the cloud based MinION analysis tools. The minoTaur package described above was used to normalize amplicons RT-PCRd from the Ebola RNA genome. They were able to prep the samples and run the sequencer in one day and analyse the data in an hour – try doing that on a HiSeq!

Taking the mobile lab deeper into the field, a combination of nanopores, mosquitoes and whatsapp (see http://ebola.nextflu.org) were used. Real-time sequencing of new cases was performed as they came into the local treatment center. The lab was a small portakabin, but the setup enabled local epidemiologists to classify cases as known, or novel, clusters. The fact that data could be returned so quickly was a significant help when there was no apparent transmission vector. It sounds crazy given that one of the scariest diseases on the planet was being sequenced on what was called Star Trek technology only a year ago.

The post Nanopore Sequencing: An Update appeared first on Bitesize Bio.

Gut Check is a periodic look at health claims made by studies and by newsmakers. We ask: Should we believe this?

The Claim: Healthy adults need eight hours of sleep each night, preferably uninterrupted, and children need a lot more.

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Khloe Kardashian’s new lifestyle book, “Strong Looks Better Naked,” is a gold mine of health and fitness advice — and, of course, lots of pictures of the reality star. STAT took a hard look at the science behind the Kardashian health tips and found, perhaps surprisingly, that many were right on point. But not all. Here’s your exclusive guide to the science behind Kardashian health mantras:

Tip 1: Add some (live) weight to your workout

When Aunt Khloe takes care of her sisters’ kids, she does squats while holding them. Wasn’t that difficult, you ask? Khloe’s response: “LOL! That was hard!”

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Pharmaceutical companies amass huge libraries of chemical compounds they can test to see if one just might be capable of being developed into a new drug. But what if, even with millions of compounds, you’re missing some that could lead to your next blockbuster treatment?

That was the idea behind Friday’s announcement that AstraZeneca and Sanofi will swap 210,000 compounds from their libraries, giving each company new compounds to screen. (It’s worth noting, as STAT Pharmalot Ed Silverman columnist points out, “the move comes as both companies struggle to replenish their product portfolios and appease restive shareholders.”)

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Scientists have used a revolutionary genetic tool to create mosquitoes unable to spread malaria, raising the possibility that lab-engineered insects could be released into the wild to stop a scourge that kills more than half a million people a year.

A team from the University of California reported Monday that they inserted genes into mosquitoes designed to block the parasite that carries malaria, and that within a few generations virtually all the insects’ descendants had inherited the antimalaria DNA.

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Illumina is to make a 5,000-genome autism database available through BaseSpace. The deal will enable researchers to analyze the genomes of people with autism and their families using tools built into Illumina's cloud computing platform.

I had planned to blast last Thursday’s news of the use of gene-editing to save a British baby from aggressive leukemia. “Two months later, Layla was cancer-free,” proclaimed one of many enthusiastic reports.

I’m always skeptical when I hear the words “cancer” and “cure” in the same sentence, let alone uttered so soon after treatment and without an accompanying technical paper so I can see the data. But when I considered the timing of unfolding events, I realized that the seemingly premature reporting of Layla’s rapidly restored health just might add an important point to the heated discussion over gene and genome editing. That is, can we keep the promising clinical applications on somatic cells, while forbidding the Frankenstein scenarios of germline manipulation?

DÉJÀ VU
Fear of novel biotechnologies is nothing new. Louise Joy Brown, the first “test-tube” baby, made headlines in 1980, regarded as somewhat of a freak until it became clear she was a normal little girl. A decade later, the first couples to select disease-free embryos after in vitro fertilization (IVF) were vilified on the Today Show. The procedures are commonly teamed today. The closest precedent to the controversy over gene editing is the famous conference to discuss recombinant DNA technology held in Asilomar, California in 1975. I was in grad school then and remember my mentor calling the objections to recombinant DNA research the “triple-headed purple monster” mindset.

I was on vacation last week when several friends emailed me the first newspaper accounts of Layla’s treatment. They were fairly uniform, as happens in this age of echo journalism, based on news releases from Great Ormond Street Hospital (GOSH) and University College London (UCL), and Cellectis, the biotech company developing the treatment.

In the rush to get those stories out, some media reports muddled gene editing and gene therapy. William French Anderson, MD, who led the first gene therapy clinical trial, in 1990, actually first uttered the idea at a journal club meeting back in 1958: “What if we found out what is wrong in sickle cell anemia? We could put in a normal globin gene and cure it!” he told me for my gene therapy book. As originally envisioned and carried out in a few thousand clinical trials, gene therapy adds a gene to compensate for a mutant one. The newer gene editing, which uses different tools, replaces or removes a gene.

I noticed right away that the first sentence of the Wall Street Journal article that several friends sent me last Thursday linked “gene-editing technique” to an article about the very gene therapy that I wrote my book about, for a form of hereditary blindness. It adds a gene that doesn’t integrate into a chromosome. Other gene therapies stick the healing genes into chromosomes somewhat randomly. Gene editing, in contrast, switches out or replaces a gene at its precise location in a chromosome. The distinction isn’t just genetic jargon — it could mean the difference between a sustained effect and one that fades as modified cells divide.

Gene editing, so far, uses enzymes to remove or swap in a very specific DNA sequence at its chromosomal home. The headline-maker is CRISPR (I’ll post an interview with its inventors soon). Layla’s treatment is the first to use TALENs. And gene editing of HIV using zinc finger nucleases has been in clinical trials since 2009. The HIV trials use the patients’ own cells, but Layla was too sick to provide enough. So instead, she received “off-the-shelf” healthy T cells from a donor, altered to attack her cancerous B cells, using CAR (“chimeric antigen receptor) technology. (T and B cells are major immune system white blood cells.) At the same time, the TALEN enzymes snipped out the genes in the donor cells whose activity would have alerted Layla’s immune system and also rendered the incoming cells resistant to a powerful chemotherapy, which could then be used to mop up any lurking cancer cells. CAR isn’t new, but using TALENs and donor cells is.

That’s huge! Layla’s treatment is precision medicine because it attacks the cancer cells only, but not personalized medicine because donor cells can help. It’s a powerful partnership that could drastically lower costs.

OUT OF OPTIONS
Layla Richards was born in June 2014 and diagnosed with very aggressive acute lymphoblastic leukemia at 14 weeks. Chemo and a bone marrow stem cell transplant hadn’t completely wiped out her cancer cells. Just before the little girl’s first birthday, Waseem Qasim, MD, Consultant Immunologist at GOSH and Professor of Cell and Gene Therapy at UCL, asked Cellectis for a special license to try its experimental product on his very sick patient. The hospital only had one vial, but the desperate request went through. The infusion took just minutes to administer, which the child didn’t even notice, said her dad.

Two weeks later, Layla developed a mild rash that reflected her body noticing the introduced cells. Over the next two weeks, fixed T cells showed up in her circulation, and their numbers climbed, there and in her bone marrow too. At the two month mark, deemed the GOSH news release, Layla was “cancer free.” She then received another bone marrow transplant just to be more certain that the cancer cells were gone. She did so well that a mere month later, she went home.

A CLOSER LOOK
Layla’s treatment is a mouthful: “Cellectis’ TALEN® gene edited allogeneic UCART19 product candidate,” or just UCART19; “U” stands for “universal.” The “CAR” — chimeric antigen receptor — is a hybrid cell-surface protein that doesn’t form naturally in the body. It’s part T cell receptor, part antibody. Like a drone and a missile, the CAR directs the T cell to a specific target, such as cancerous B cells or HIV-infected cells. (I guest-blogged about it here.)

I spoke with Bruce Levine, PhD, the Barbara and Edward Netter Professor in Cancer Gene Therapy at the Perelman School of Medicine and a pioneer of CAR technology, at a conference in January, 2013. The New York Times had just published a piece about one of his patients, another little girl who had an astonishing recovery from the same type of leukemia, 6-year-old Emma Whitehead. The Times article appeared the day before co-inventor Carl June presented the data at a major conference, and he was a little surprised to be in the position where his audience already knew of the case, Dr. Levine recalled. But that data presentation and media coverage was 9 months after the treatment.

The CAR effect lasts. Emma, more than 3 years later, “is doing fantastic,” Dr. Levine just told me. “This year so far she has met President Obama, Tom Brokaw, and Heidi Klum!” Unlike Layla, Emma’s own cells were used.

The idea to arm T cells to attack cancerous B cells wasn’t new, even when Emma made headlines. “Zelig Eshhar at the Weitzmann Institute in Israel published a paper in 1989 that you can combine an antibody with a signal,” Dr. Levine said. The Penn group has deployed CARs in clinical trials against HIV, and more recently a case of multiple myeloma.

Despite the frequent use of “cancer-free” and “breakthrough” in the news coverage of Layla and her vanishing leukemia, the quotes were appropriately qualified. “We have only used this treatment on one very strong little girl, and we have to be cautious about claiming that this will be a suitable treatment option for all children. But, this is a landmark in the use of new gene engineering technology and the effects for this child have been staggering,” said Dr. Qasim in the news release. Clinical trials needed to add evidence that it was the gene editing and not the chemo or the stem cell transplant that led to remission likely will begin in 2016.

TIMING

Three months may seem way too soon to report even startling results on a single cancer patient. “Cancer-free” is usually evoked only 5 years after successful treatment, and I wouldn’t even use it then.

Of course I hope Layla stays well, but I can’t help but recall the little girl treated for HIV infection with antiretrovirals shortly after birth and widely declared HIV-free when the researchers published 2 years later. By age 4, the virus had re-emerged, leading to such headlines as “Girl who was declared ‘functionally cured’ of HIV now has active virus”.

So why issue the news release about Layla so soon? It’s not as if there aren’t already treatments for leukemia. And a patient can’t just go and order her complex treatment at the local clinic.

The timing of the announcement may be important when we look back on the birth of gene and genome editing, just as we did 40 years ago for the recombinant DNA technology that has given us many useful drugs.

The news releases came out Thursday, November 5, as Layla and her family appeared on television throughout Britain. That was also the day that abstracts were published online for the American Society of Hematology annual meeting, to be held December 5-8 in Orlando. Cellectis’s stock rose, 11% after the news broke and another 3% the next day.

But between November 5 and December 5 will be another meeting, the International Summit on Human Gene Editing to be held in Washington, D.C. December 1-3. And that may be where Layla’s story has its greatest impact.

The international summit, called for in September with a stellar planning committee, will focus on scientific as well as ethical and societal issues that might arise if gene editing is used to alter the human germline, which would transmit a change to the next generation. That’s something that most nations have banned, but researchers in China have already done, albeit on doomed human embryos. That work was published last April 1, but was most definitely not a joke.

I hope that Layla’s remission is forever, and that her story can help to preserve a technology that has such enormous potential for treating or even preventing cancer, infectious disease, and genetic disease. Let’s not throw the baby out with the bathwater.