Dévelopements en Science et Technologie

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During the course of its duties, the BWC Implementation Support Unit becomes aware of various developments in the life sciences that could be relevant to efforts to review advances under the current work programme. Such advances are recorded below.

Understanding of pathogenicity, virulence, toxicity, immunology and related issues:

• Scientists have demonstrated that it is possible to make the H7N9 influenza virus (that continues to infect animals and people and for which gain-of-function studies for mammalian transmission are planned) resistant to anti-viral drugs without impacting its virulence. See the paper: Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility, in Nature Communications, published 10 December 2013, added 11 December 2013.

• Scientists discover new type of botulinum toxin but delay publishing sequence data due to DURC. Dover et al, describe a new type of biotulinum toxin the paper, Molecular Characterization of a Novel Botulinum Neurotoxin Type H Gene, published in the Journal of Infectious Diseases. A second paper in the same journal, A Novel Strain of Clostridium botulinum That Produces Type B and Type H Botulinum Toxins, by Barash and Arnon details that the Type H Botulinum Toxin “by use of the standard mouse bioassay, could not be neutralized by any of the Centers for Disease Control and Prevention–provided monovalent polyclonal botulinum antitoxins raised against BoNT types A–G.” The two papers were accompanied by a pair of editorials: one by Popoff describing the historical context and scientific importance of the observations(Botulinum Neurotoxins: More and More Diverse and Fascinating Toxic Proteins); and the other by Relman discussing the issues related to dual use research of concern (DURC) raised by these articles (“Inconvenient Truths” in the Pursuit of Scientific Knowledge and Public Health). There was also a useful summary by Hooper and Hirsch (Novel Clostridium botulinum Toxin and Dual Use Research of Concern Issues). (Added 11 October 2013)

• Fouchier et al, Gain-of-Function Experiments on H7N9, Science, Nature,http://www.nature.com/nature/journal/v500/n7461/full/500150a.html,http://www.sciencemag.org/content/341/6146/612.full, is a letter from 22 leading influenza researchers indicating their intention to perform gain-of-function research with the H7N9 influenza virus. The paper details plans to enhance the wild viruses’ host range, make it more suited for transmission in mammals, make it resistant to therapeutics, make transmit better amongst mammals and increase its pathogenicity. Accompanying editorials, Handle with care in Nature,http://www.nature.com/news/handle-with-care-1.13505, and Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies in Science, http://www.sciencemag.org/content/341/6146/601.full, both illustrate that there is no consensus on the need for the research and explore calls for robust reviews of potential risks. (Added 9 August 2013)

• Morens et al, Pandemic Influenza Viruses – Hoping for the Road Not Taken, New England Journal of Medicine, http://www.nejm.org/doi/full/10.1056/NEJMp1307009, details the difficulties in assessing evolutionary pathways leading to pandemic influenza. This paper also looks back at past pandemics over the last century and uses them to provide perspectives on recent and ongoing influenza outbreaks. (Added 9 August 2013)

• Nathanael Johnson – Genetically engineered food: Allergic to regulations?,http://tinyurl.com/p5bx7ow, This blog post, in everyday language, examines efforts to assess risk from allergens from GM food. They seem to struggle with many of the same issues as when trying to assess risk connected to pathogenicity, virulence, toxicity, etc., especially how to deal with the introduction of material not previously identified as being relevant, as well as impact of modulation of the metabolism of the recipient organism. There may be interesting insights here for S&T discussions in 2014. (Added 31 July 2013)

• Coggeshall et al – The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax,http://onlinelibrary.wiley.com/doi/10.1111/jcmm.12075/abstract. This paper suggests that death in inhalation anthrax results from an overwhelming bacteraemia that leads to severe sepsis. (Added July 2013)

• Bradley-Stewart et al, Cytokine responses in patients with mild or severe influenza A(H1N1)pdm09,http://www.sciencedirect.com/science/article/pii/S1386653213001911. This paper examines the role of extreme immune responses in severe influenza cases. (Added July 2013)

• Schnirring, New H7N9 studies yield pathogenicity clues, http://www.cidrap.umn.edu/news-perspective/2013/07/new-h7n9-studies-yield-pathogenicity-clues, A review of three recent papers providing insights into the pathogenicity of H7N9. (Added July 2013)

Enabling technology:
Engineering biological systems and networks

• Oye et al., in the paper Regulating Gene Drives, provide an overview of the potential environmental and security impact of the use of gene drive techniques, and outline a series of policy and regulatory recommendations for the responsible development of the technique. A technical overview of gene drives is provided in a paper by Esvelt et al., Concerning RNA-guided gene drives for the alteration of wild populations, published in eLIFE. (Added 21 July 2014)

• Payne et al, in the paper Temporal control of self-organized pattern formation without morphogen gradients in bacteria, in the journal Molecular Systems Biology demonstrate that an engineered gene circuit can act as a timing mechanism to create a predictable ring growth pattern that adjusts to the size of its environment. (Addedd 11 October 2013)

Advances in dealing with disease:
Therapeutics

• Novel antibiotics – Kyoung Hwa Jang et al, Anthracimycin, a Potent Anthrax Antibiotic from a Marine-Derived ActinomyceteAngewandte Chemie International Edition,http://dx.doi.org/10.1002/anie.201302749, details the discovery of an entirely new class of antibiotic – Anthracimycin. The paper details significant activity toward Bacillus anthracis and illustrates how to manipulate the drug so it retains activity against Gram-positive bacteria, such as anthrax, but also shows activity against selected Gram-negative bacteria. (Added 6 August 2013)

• Antimicrobial resistance – Maryn McKenna’s Nature News Feature, http://tinyurl.com/qheyzp3, describes the emergence of carbapenem-resistant Enterobacteriaceae (CREs). These bacteria “evade the action of almost all antibiotics — including the carbapenems, which are considered drugs of last resort”. The article also includes insights and views from various public health experts on the nature of the threat posed by the development of this anti-biotic resistance as well as options for dealing with it. (Added 2 August 2013)

Prevention and prophylaxis

• Smith et al – Development of influenza H7N9 virus like particle (VLP) vaccine: Homologous A/Anhui/1/2013 (H7N9) protection and heterologous A/chicken/Jalisco/CPA1/2012 (H7N3) cross-protection in vaccinated mice challenged with H7N9 virus,http://dx.doi.org/10.1016/j.vaccine.2013.07.043. This paper describes a virus like particle created to contain key regions of the H7N9 virus. This vaccine candidate showed great promise of protecting against the disease in mice. (Added 31 July 2013)

• Marohn and Barry, Live attenuated tularemia vaccines: Recent developments and future goals,http://dx.doi.org/10.1016/j.vaccine.2013.05.096. The paper review recent advances in creating vaccines for this infectious disease, which has in the past been developed as a biological weapon. (Added July 2013)

Diagnostics

• Genetic engineering News, Complimentary Webinar: Inline Automation and Miniaturized Reaction Volumes for Real Time Isothermal DNA Amplification, Wednesday 17 July 2013,http://www.genengnews.com/webinars/inline-automation-and-miniaturized-reaction-volumes-for-real-time-isothermal-dna-amplification/210/. The webinar provides information on a highly-automated, high-throughput inline data-generating system for real-time PCR. The platform reportedly makes it possible to go from a sample to answer in 20 minutes. Real-time PCR is increasingly used as a diagnostic tool. (Added July 2013)

Production, dispersal and delivery technologies:

• Buckley et al, Genetic Barcodes for Improved Environmental Tracking of an Anthrax Simulant,http://aem.asm.org/content/78/23/8272.full . A mechanism for effectively tracking agents following an environmental release “providing specific artificial detection signatures”. (Added July 2013)

• Emanuel et al, Detection and Tracking of a Novel Genetically Tagged Biological Simulant in the Environment, http://aem.asm.org/content/78/23/8281.full . A proof of principle study of the Buckley et al paper, using an anthrax simulant. (Added July 2013)

 

Basic Science:

• Gene Switches Do More Than Flip ‘On” or ‘Off”: Can Exhibit Much More Complex Binding behavior,http://www.sciencedaily.com/releases/2012/04/120411131911.htm

• Running to stand still, http://www.nature.com/nature/journal/v484/n7393/full/484171a.html

• ‘Junk DNA’ Defines Differences Between Humans and Chimps,http://www.sciencedaily.com/releases/2011/10/111025122615.htm

• The New Cell Anatomy, http://www.nature.com/news/cell-biology-the-new-cell-anatomy-1.9476

• DNA replication caught in the Act,http://www.nature.com/nature/journal/v487/n7406/full/487177a.html

• Watching DNA polymerase n make a phosphodiester bond,http://www.nature.com/nature/journal/v487/n7406/full/nature11181.html

• Noncoding RNAs decapped, http://www.nature.com/nature/journal/v483/n7387/full/483009e.html

• RNA Advances Reshape Prevailing Wisdom, http://www.genengnews.com/gen-articles/rna-advances-reshape-prevailing-wisdom/4039/

• More Evidence Found for Quantum in Photosynthesis,http://www.wired.com/wiredscience/2011/12/quantum-physics-photosynthesis/

• Architecture Reveals Genome’s Secrets, http://www.the-scientist.com/?articles.view/articleNo/33366/title/Architecture-Reveals-Genome-s-Secrets/

• High order chromatin architecture shapes the landscape of chromosomal alterations in cancerhttp://www.nature.com/nbt/journal/v29/n12/abs/nbt.2049.html

• Three Dimensional Genome Architecture Influences Partner Selection for Chromosomal Translocations in Human Disease,http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0044196

• Disease-specific gene repositioning in breast cancer, http://jcb.rupress.org/content/187/6/801

• Topological domains in mammalian genomes identified by analysis of chromatin interactions,http://www.nature.com/nature/journal/v485/n7398/full/nature11082.html

• Spatial partitioning of the regulatory landscape of the X-inactivation centrehttp://www.nature.com/nature/journal/v485/n7398/full/nature11049.html

• Comprehensive Mapping of Long Range Intercations Reveals Folding Principles of the Human Genomehttp://www.sciencemag.org/content/326/5950/289.short

Mechanisms of Diseases:
Emerging and Re-emerging Diseases

• Discovery of an Ebolavirus-Like Filovirus in Europe, http://www.ncbi.nlm.nih.gov/pubmed/22039362

• Identification of a Novel Bat Papillomavirus by Metagenomics,http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0043986

Immune System

• Calming the cytokine storm, http://www.nature.com/nature/journal/v477/n7365/full/477373d.html

• Drugs give the immune system a mistaken sense of selfhttp://arstechnica.com/science/2012/05/drugs-give-the-immune-system-a-mistaken-sense-of-self/

• Immune self-reactivity triggered by drug-modified HLA-peptide repertoirehttp://www.nature.com/nature/journal/vaop/ncurrent/full/nature11147.html

Pathogens and Hosts

• Imaging of Bubonic Plague Dynamics by In Vivo Tracking of Bioluminescent Yersinia pestishttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0034714

Prion Diseases

• Proteins behind mad-cow disease also help brain to develop http://www.nature.com/news/proteins-behind-mad-cow-disease-also-help-brain-to-develop-1.12428

• Axonal prion protein is required for peripheral myelin maintenancehttp://www.nature.com/neuro/journal/v13/n3/abs/nn.2483.html

Detection:
Detecting Disease event

• DNA to Hang Your Hat On, http://www.genengnews.com/insight-and-intelligence/dna-to-hang-your-hat-on/77899783/

Tracking, Surveillance & Epidemiology

• Did Advances in Global Surveillance and Notification Systems Make a Difference in the 2009 H1N1 Pandemic? – A Retrospective Analysis,http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0059893

Diagnosis Prior to Symptons

• New Test to spot diseases early http://articles.timesofindia.indiatimes.com/2012-05-29/science/31887014_1_diseases-biomarker-early-diagnosis

Diagnostics:
Cheap Equipment

• Cheap and quick HIV testing made possible with DVD scanners, http://phys.org/news/2013-04-cheap-quick-hiv-dvd-scanners.html

Point of care Diagnostics

• Differentiation between Viral and Bacterial Acute Infections Using Chemiluminescent Signatures of Circulating Phagocytes, http://pubs.acs.org/doi/abs/10.1021/ac200596f

Accuracy

• Routine Use of Microbial Whole Genome Sequencing in Diagnostic and Public Health Microbiology,http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002824

Prevention:
New Vaccines

• Developing Next-Gen Conjugate Vaccines, http://www.genengnews.com/gen-articles/developing-next-gen-conjugate-vaccines/4042/

Novel Approaches

• Bacteria bore through biofilms, http://www.nature.com/nature/journal/v487/n7406/full/487143c.html

Drug Deliveries

• Silk stabilizer may eliminate need to refrigerate vaccines and antibioticshttp://biomedicalresearchnews.wordpress.com/2012/07/20/silk-stabilizer-may-eliminate-need-for-refrigeration-of-vaccines-and-antibiotics/

Production Technology

• FDA approves first flu vaccone grown in insect cells http://www.cidrap.umn.edu/news-perspective/2013/01/fda-approves-first-flu-vaccine-grown-insect-cells

Therapeutics:
Novel Antibiotics

• Bacterial signal to survive, http://www.nature.com/nature/journal/v483/n7390/full/483377a.html

Novel Antivirals

• Neuraminidase inhibitor suscetibility surveillance of influenza viruses circulating worldwide during the 2011 Southern Hemisphere season,http://sciencealerts.com/stories/2265464/Neuraminidase_inhibitor_susceptibility_surveillance_of_influenza_viruses_circulating_worldwide_during_the_2011_Southern_Hemisphere_season.html

Toxin Therapeutics

• Humanization and Characterization of an Anti-Ricin Neutralization Monoclonal Antibodyhttp://www.plosone.org/article/metrics/info%3Adoi%2F10.1371%2Fjournal.pone.0045595;jsessionid=DB548218FBEEC1335B8F08A993EACBD5

Anti-Prion Therapeutics

• Potential Prion Disease Therapy Uncovered http://www.genengnews.com/gen-news-highlights/potential-prion-disease-therapy-uncovered/81248178/

Novel Approaches

• New Compounds Defeats Drug-Resistant Bacteriahttp://esciencenews.com/sources/science.daily/2011/11/28/new.compound.defeats.drug.resistant.bacteria

Counterfeit Therapeutics

• New handheld Device Detects Counterfeit Anti-Malaria Drugs,http://www.fda.gov/downloads/NewsEvents/Newsroom/FactSheets/UCM349286.pdf

Antimicrobial Resistance

• Emergence of Resistance, http://www.genomeweb.com/print/1224836?hq_e=el&hq_m=1577

Response:
Restricting Spread

• Preventing Pandemics Via International Development: A Systems Approach

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001354

Decontamination

• Lab-Scale Assessment to Support Remediation of Outdoor Surfaces Contaminated with Bacillus anthracis Spores

http://www.omicsonline.org/2157-2526/2157-2526-2-110.php

Efficiency of Response

• Changes in and shortcomings of control strategies, drugs stockpiles, and vaccine development during outbreaks of avian influenza A H5N1, H1N1, and H7N9 among humans,http://www.biosciencetrends.com/action/downloaddoc.php?docid=656