Pandora Report: 11.22.2019

Happy Antibiotic Awareness Week! Are you being a good steward of antimicrobials during this respiratory virus season?

When A Lab Explosion Ruins Your Day – Stories of Vector 
A few months back, an explosion at the Russian laboratory complex known as the State Research Centre of Virology and Biotechnology (Vector), raised a red flag regarding the stockpiling of smallpox and realistically, biosafety/biosecurity. Not surprisingly, stories about where the explosion occurred, what was kept in that area, and all manner of horror movie-esque plots began to swirl. Gwyn Winfield though, has broken down the rumors, the realities, and the challenges of understanding what exactly happened when well, there’s not a lot of trust in Russian explanations. Gwyn takes care to highlight how fast speculation occurred though, and that while it may not have been easy to get answers right away, the theatrics of lab-to-bioweapon speculation does little good. Noting that the blast occurred on the 5th floor of building one – “The floor had been under repair since July, and since there was no research in progress there, and the area was not secure, there were no pathogens on that floor to be released.” As Winfield notes, the lack of information makes things challenging and while experts might make guesses, “the individuals that need to take the most lessons from this are exercise planners, globally but especially in Russia”. You can read the full article here.

The Microbiome and AMR
Microbiota bear effects on a variety of chronic diseases such as gastrointestinal, autoimmune, respiratory, neurological, and cardiovascular conditions; however, the microbiome also plays a role with infectious diseases. The growing body of research on the importance of the microbiome to human health links natural flora and the immune system, which are in a largely symbiotic relationship. More specifically, a healthy microbiome aids in the induction, training, and function of the immune system and, in return, the immune system maintains a happy balance between natural flora and the host human. Unfortunately, that relationship is under great threat as the persistent overuse of antibiotics destroys not only the invasive bacteria but also the healthy bacteria that help maintain immune function. Antimicrobial resistance (AMR) is ability of microbes – bacteria, viruses, fungi – to circumvent the mediating effects of antibiotic, antiviral, and antifungal therapeutics. The overuse of antibiotics enables strong, resistant bacteria to survive in the host, so your gut ultimately populates with mostly resistant bacteria, even bacteria resistant to multiple drugs. Disruptions to the microbiome by antibiotic use adds to the spread and strength of antimicrobial resistance in harmful microbes. Our overreliance on the prescription of antibiotics to alleviate bacterial infections, even minor ones that the immune system may be able to overcome, and a lack of medication compliance resulting in misuse are chipping away at the clinical efficacy of these drugs. This is of considerable concern as microbes become cleverer and less susceptible to multiple medications, resulting in infections that are less and less treatable. According to the CDC, there are over 2.8 million antibiotic-resistant infections in the US each year and more than 35,000 people die from those infections. The critical task at hand is to develop alternative therapeutics that can treat infections while, at least, not contributing to further microbial resistance. As a mediator for colonization resistance and a symbiote of the immune system, the microbiome possesses potential as a therapeutic gateway to subvert resistance.

Biodosimetry Biomarkers and Serum Proteomic Signatures – GMU Biodefense Alum Tackles It All 
GMU Biodefense doctoral student Mary Sproull is our resident guru on radiation – she’s a biologist in the Radiation Oncology Branch of the National Cancer Institute at NIH. Here are just two more reasons why Sproull is the go-to person for things like biodosimetry: she has two new publications that you’ll want to check out. The first, Comparisons of Proteomic Biodosimetry Biomarkets Across Five Different Murine Strains (try saying that five times fast) “seeks to compare the expression levels of five previously established proteomic biodosimetry biomarkers of radiation exposure, i.e., Flt3 ligand (FL), matrix metalloproteinase 9 (MMP9), serum amyloid A (SAA), pentraxin 3 (PTX3) and fibrinogen (FGB), across multiple murine strains and to test a multivariate dose prediction model based on a single C57BL6 strain against other murine strains.” Make sure to read this study as it discusses why these strain specific differences exist between expression levels. In the second article A Serum Proteomic Signature Predicting Survival in Patients with Glioblastoma, Sproull and the research team discuss this common brain tumor and how developing adequate biomarkers can help drive stronger patient outcomes. “Analysis of potentially relevant gene targets using The Cancer Genome Atlas database was done using the Glioblastoma Bio Discovery Portal (GBM-BioDP). A ten-biomarker subgroup of clinically relevant molecules was selected using a functional grouping analysis of the 40 plex genes with two genes selected from each group on the basis of degree of variance, lack of co-linearity with other biomarkers and clinical interest. A Multivariate Cox proportional hazard approach was used to analyze the relationship between overall survival (OS), gene expression, and resection status as covariates.”

Gene Editing
Advancements in biotechnology pose potentials and perils as such technology becomes easier to access and use by a wide array of bio-users, not just formally trained scientists at professional laboratories. Gene editing, the alteration of an organism’s DNA, is one such biotechnology. A number of research and government entities are working diligently to maximize the potential benefits of gene editing while simultaneously minimizing its perils. Two such entities are the National Academies of Sciences, Engineering, and Medicine and the Defense Advanced Research Projects Agency (DARPA). The former is concerned with perils of synthetic biology while the latter is trying to unlock its potential. The National Academies of Sciences, Engineering, and Medicine just released Strategies for Identifying and Addressing Vulnerabilities Posed by Synthetic Biology: Proceedings of a Workshop in Brief, which summarizes the key discussions in an October 2018 meeting of experts and policymakers following a report for the DOD, Biodefense in the Age of Synthetic Biology. The meeting’s purpose was to assemble federal personnel and the committee for the DOD report to consider the implications for actions DOD might take to quell potential misuse of synthetic biology capabilities. The committee evaluated 12 capabilities associated with (1) the synthesis and modification of pathogens; (2) production of chemicals, biochemicals, and toxins; and (3) modulation of human physiology. Each of the three capability areas were assigned relative levels of concern in terms of the usability of a technology, its usability as a weapon, its requirements of actors, and the potential for its mitigation. Additional workshop discussions included the potential of delivery mechanisms to serve as a barrier to the misuse of synthetic biology to produce weapons, the possibility to use synthetic biology to modify human physiology in new ways, and opportunities in computational biology to alleviate fears about synthetic biology capabilities through the prevention, detection, and attribution of its misuse. DARPA’s latest biotechnology project is the “Detect It with Gene Editing Technologies” program, more lovingly called DIGET. The primary objective of DIGET is “to provide comprehensive, specific, and trusted information about health threats to medical decision-makers within minutes, even in far-flung regions of the globe, to prevent the spread of disease, enable timely deployment of countermeasures, and improve the standard of care after diagnosis.” The DIGET dream deliverables are two devices: (1) a handheld and disposable point-of-need tool that simultaneously screens 10 or more pathogens or host biomarkers and (2) a multiplexed detection platform that simultaneously screens at least 1,000 clinical and environmental samples. DIGET seeks to incorporate gene editors and detectors biosurveillance as well as swift point-of-need diagnostics for endemic, emerging, and engineered pathogens. DARPA is hosting a Proposer’s Day meeting about the DIGET program on 11 December 2019.

Biological Threats to U.S. National Security – Subcommittee on Emerging Threats and Capabilities 
On Wednesday, Dr. Thomas V. Inglesby, Dr. Tara J. O’Toole, and Dr. Julie Gerberding gave testimony to this subcommittee within the U.S. Senate Committee on Armed Services. During the testimony, Dr. Inglesby “noted the growing threat of biological events that can emerge from nature, deliberate attack, or accidental release and reviewed current US government efforts in this arena. He presented recommendations to improve the government’s response to and preparedness for a major biological event.” You can read his full testimony here.

Revisiting the Biological Weapons Convention Protocol
Lynn Klotz recently wrote on the gaps within the BWC in relation to compliance monitoring. Despite efforts to change this in the past, those pushing for a protocol to randomly select site visits as means to do quality checks, have been disappointed over the years as administrations cite that such additions would not truly verify or provide greater security. As Klotz underscores – this sentiment fundamentally misses the goal of the protocol…which is transparency. “But recent events serve to underscore that a protocol to the convention to address the treaty’s shortcomings is an idea that should be revisited. Unfounded Russian allegations about biological weapons development in former Soviet countries are threatening the effectiveness of the convention. This concern along with strong arguments for the high importance of transparency in international treaties calls for revisiting the protocol, which had provisions for both transparency and for dealing with allegations like Russia’s.” Citing the 2019 meeting in which Russia alleged that several former Soviet states had active bioweapons programs, distrust soon grew and disruption rippled throughout the BWC. Klotz emphasizes that this exact situation is a prime reason why a protocol should be revisited – to help build confidence through increasing transparency. Not a free-for-all, but rather through managed-access rules, such as random visits by inspection teams would help verify the absence of bioweapons. Klotz takes care to discuss why protocol efforts were abandoned in 2001 and the role of transparency in multilateral arms control regimes, which you can read more about here.

GMU Hosts Health Security Career Panel 
Last week, adjunct professor Ashley Grant, a lead biotechnologist at the MITRE Corporation, held a career panel at the Schar School of Policy and Government at George Mason University as part of her course on Global Health Security Policy. To highlight the different paths that graduate students in the Biodefense program can take in the health security field, Professor Grant convened a diverse panel of health security practitioners to discuss their jobs and the skills they have needed to succeed. The panel included professionals from a variety of different backgrounds ranging from local health providers to Federal employees. Students in the Schar School’s Biodefense Graduate Program were able to ask the panelists about the challenges of moving from a technical career path into science policy and opportunities for internships. The panel included Stuart Evenhaugen of the Assistant Secretary for Preparedness and Response (ASPR)’s Strategy Division in the Department of Health and Human Services (HHS); Syra Madad, the Senior Director of System-Wide Special Pathogens Program at NYC Health + Hospitals; Halley Smith, a program lead with the U.S. Department of State Cooperative Threat Reduction Program, on detail from Sandia National Laboratories Global Chemical and Biological Security Program; Sapana Vora, the Deputy Team Chief for the U.S. Department of State’s Biosecurity Engagement Program (BEP) and Iraq Program in the Office of Cooperative Threat Reduction (CTR); and Malaya Fletcher, a Lead Scientist at Booz Allen Hamilton in Washington, DC.  The panel also included LTC Justin Hurt a CBRN/WMD Organizational Integration Officer in the Army G-3/5/7 Office who is currently enrolled in the Biodefense PhD program. As biodefense graduate student Michael Krug noted, “The panel was immensely valuable in providing detailed insights and experiences into each of the panelist’s unique career paths. Emphasizing the demand for multi-disciplined approaches, as well as active communication to answer the many health security questions facing the world.”

A Little Bit of Plague and A Whole Lot of Panic  
Plague – a word that still sparks fear after hundreds of years. Two cases were recently reported in China’s Inner Mongolia and of course, it involved a hunter and butchering/eating a wild animal. Diagnosed on November 5th, there were two additional cases reported in Beijing but from the Inner Mongolia area. “In both cases, the two patients from Inner Mongolia were quarantined at a facility in the capital after being diagnosed with pneumonic plague, health authorities said at the time. The Inner Mongolia health commission said it found no evidence so far to link the most recent case to the earlier two cases in Beijing.” As many have pointed out, the fear around this news has been more damaging to response efforts. Pneumonic plague is not as highly contagious as many news outlets have let on – only requiring Droplet + Standard isolation precautions and plague is easily treatable with antibiotics or prophylaxis.

Should We Be Celebrating CRISPR’s Anniversary?
It’s not many times an expert and innovator writes an article entitled “CRISPR’s unwanted anniversary” about a tech they were instrumental in developing. Dr. Jennifer Doudna recently wrote on those moments that can make or break a disruptive technology and in the case of CRISPR, it was last year, when Hong Kong-based scientist He Jiankui started the CRISPR baby drama. This was a pivotal moment in not only biotech, but also genome editing and its future. As Doudna notes, it’s comforting that scientists around the world reacted with conversations about the need for safeguards and transparency as CRISPR technology grows. In the face of this anniversary though, what has been done? Are there consequences for going against widely accepted norms? Doudna leaves us with the notion that “The ‘CRISPR babies’ saga should motivate active discussion and debate about human germline editing. With a new such study under consideration in Russia, appropriate regulation is urgently needed. Consequences for defying established restrictions should include, at a minimum, loss of funding and publication privileges. Ensuring responsible use of genome editing will enable CRISPR technology to improve the well-being of millions of people and fulfill its revolutionary potential.”

Outbreak Dashboard
In keeping up with the latest outbreaks, here are some quick updates on a handful of the infectious disease events that are going on  – The outbreak of Ebola virus disease in the DRC may be slowing as there were no new cases reported on November 19th but over 400 suspected cases were still being assessed (total case count is 3,296). With the recent approval of the Ebola vaccine by the European Medicines Agency (EMA), the distribution of the vaccine will increase and could impact the outbreak as well. Nigeria is facing a Yellow Fever outbreak, which it has struggled against since 2017. In the past 4 weeks, 839 new cases have been reported. Flu activity is increasing in the United States and the predominant strains are B/Victoria, A(H3N2) and A(H1N1)pdm09. 2.3% of healthcare provider visits in outpatient settings were for influenza-like illnesses. There is also a new E. coli outbreak linked to pre-packaged chicken Caesar salads impacting 17+ people across 8 states.

Hot Spots and Inadequate Monitoring for Bioterrorism – An American Story
Law professor Ana Santos Rutschman of Saint Louis University recently wrote on the usual and unusual biological suspects and how organisms like Salmonella can easily be overlooked as cases of bioterrorism (case in point the 1984 Oregon attack). Rutschman delves into preparedness efforts, like BioWatch, and how “there is a profound lack of coordination between federal agencies and local communities. When asked about what happens after notifications of a possible bioterrorism attack, Dr. Asha George, executive director of the Bipartisan Commission on Biodefense, answered: “They go off but nobody knows what to do.”

Stories You May Have Missed:

• Ongoing Outbreaks Trigger Laws to Limit Vaccine Exemptions – in the middle of measles outbreaks and pertussis cases occurring frequently, there is a desperate need for reducing vaccine exemptions that protect the anti-vaccine instead of the public’s health. “In 2018, the same research group published a study showing that, despite rising numbers of proposed antivaccine laws, pro-vaccine bills were more likely to become law. For the current study, the team looked at how health data might affect laws. The new findings come following a surge of measles activity in the United States this year, mostly fueled by a few large outbreaks that nearly cost the nation the measles elimination status that it achieved in 2000.”
• Acinetobacter Baumannii Risk Factors– “After assessing 290 isolates, they found that 169 were endemic (96 of REP-1) and the most common site for isolation was the respiratory tract. In total, 109 patients (37%) had only Acinetobacter baumannii isolated, while some had up to 5 other organisms also identified. In those colonized, 69 were REP-1, and 64 with REP-2-5, the research team found that for those patients with REP-1, there was a 70% increase in carriage per increase in Schmid score (statistically significant), and a 50% increase in REP-2-5. Interestingly, prior colonization, longer lengths of stay, and immunosuppression did now have a statistically significant relationship with Acinetobacter baumannii colonization. “