Pandora Report 3.10.2017

Looking for a great podcast on CRISPR? Check out RadioLab – they also have a captivating one on patient zeroes throughout history!

Summer Workshop on Pandemics, Bioterrorism, and Global Health Security: From Anthrax to Zika 
If you’re looking to learn more about global health security, synethic biology, biosecurity, and what exactly “biodefense” entails, you’ll want to mark your calendar for the GMU Biodefense three-day, non-credit summer workshop on July 17-19, 2017! Participants will look at the challenges facing the world at the intersection of national security, public health, and the life sciences. Instructors for the workshop range from FBI special agents to biodefense professors and USAMRIID commanders. The workshop will look at the spectrum of biological threats – including naturally occurring disease outbreaks such as SARS, Zika, and Ebola, lapses in biosafety, dual-use research of concern, and the threat of bioterrorism. From now until May 1st, you can take advantage of the early bird registration discount!

Glaring Gaps: America Needs A Biodefense Upgrade
GMU biodefense PhD alum Daniel M. Gerstein is emphasizing the need to strengthen American biodefense capabilities. “Recent legislation has called for a comprehensive biodefense strategy. If carried out in a thorough and systematic way, and properly funded, this will be a great improvement for the country and the world.” Gerstein notes that while the National Defense Authorization Act for Fiscal Year 2017 called for a joint biodefense effort, there is still a desperate need for a structured and systematic approach. Perhaps one of the biggest issues Gerstein found is the current view of biodefense as a series of programs. Approaching global health security threat requires us to view biodefense as a complex system, not a series of programs. To fix the glaring gaps in U.S. biodefense efforts, he notes that any remedy will have to accept the complexity of the problem and that there is no single panacea. Internal coordination, improvement of diagnostics and treatment, and technology management are all things that must be addressed to strengthen American biodefense. “Export controls in the United States, for example, actually hinder international collaboration. Exchanging pathogen strains used in the development of medical countermeasures, diagnostics, and bio-surveillance remains difficult – even, at times, for close international partners. In one case, the United States was attempting to share a strain of the Ebola-Reston pathogen with the government of Australia, but export laws prevented this sharing, so the strain was instead acquired from the Philippines, where the strain originated.” While we’ve made great strides since the Amerithrax attacks, there is much to be done to create a systematic and resilient biodefense strategy.

Chemical Weapons Reportedly Used in Mosul
The WHO has recently activated an emergency response plan with several partners to help treat twelve people for potential exposure to chemical weapons in Iraq. “Lise Grande, the UN humanitarian coordinator in Iraq, called for an investigation. ‘This is horrible. If the alleged use of chemical weapons is confirmed, this is a serious violation of international humanitarian law and a war crime, regardless of who the targets or the victims of the attacks are,’ she said in a statement.” Many are pointing to ISIL as the likely culprit since they hold the majority of west Mosul and have a history of rudimentary use of chemical weapons.

China’s Growing Bird Flu Worries  
Despite a recent surge in human A(H7N9) cases, the WHO has stated that the risk of an epidemic remains low. Even with this release, the development of two distinct strains in a disease that has a mortality rate hovering around 30%, has many worried. “That will probably force development of a second small stockpile of emergency vaccine to be rolled out if the virus becomes more transmissible and threatens to turn into a pandemic, a scientist at the Centers for Disease Control and Prevention said. Flu specialists from around the world gathered in Geneva this week to assess the global influenza situation and discuss with vaccine companies which viral strains should be in next winter’s flu shots. China has had 460 lab-confirmed human cases of H7N9 bird flu this winter, said Dr. Wenqing Zhang, head of the W.H.O.’s global influenza program. That is the most in any flu season since the first human case was found in 2013.” Interestingly, around 7% of the new H7N9 cases were resistant to drugs like Tamiflu, which has many researchers working to make a H7N9 seed vaccine, including a secondary one due to the split strains. Coming on the heels of this outbreak, US officials have announced that highly pathogenic avian influenza (HPAI) was found in a commercial poultry farm in Tennessee. 700 birds died from infection and almost 73,000 were destroyed. The farm is a contracted supplier of chicken meat for the U.S.’s biggest supplier, Tyson, which released an announcement on March 5th regarding testing of local birds, etc.

Global Health Security Index Development
Johns Hopkins Center for Health Security recently received a grant from the Open Philanthropy Project and the Robertson Foundation to coordinate with the Nuclear Threat Initiative (NTI) and the Economist Intelligence Unit (EIU) to develop a Global Health Security Index. “The mission of the index is to encourage progress towards a world that is capable of preventing epidemics of international impact (either natural, accidental or deliberate) from arising, or, should, prevention fail, respond quickly to contain them.” The first phase of the project will aim at developing framework that can measure a country’s level of health security. While the GHSA and JEE are processes to increase transparency, preparedness, and country capabilities, the goal of this index is to fill the gaps in motivation and also the factors that are not in the hands of the health sector.

Antimicrobial Resistance in Pets: Are We Ignoring A Looming Threat? 
GMU biodefense PhD student Saskia Popescu is looking at the threat of antibiotic resistance, but from a somewhat forgotten patient population – our pets. The recent WHO list of worrisome antimicrobial resistant bugs has drawn a lot of attention to the growing threat of an antibiotic apocalypse however, sometimes it takes a personal experience to look outside the box. Pulling from experiences of dealing with drug resistance in her dog to the loss of SeaWorld’s controversial orca, Tilikum, Popescu notes the rising threat of AMR brewing in domesticated animals. Sadly, it seems that many veterinarians and infectious diseases researchers have been drawing attention to the role of household animals in antimicrobial resistance and yet, just like the human issue, it’s not getting the attention it deserves. In her article, Popescu points to the need to start addressing the full circle of microbial resistance, starting with our furry friends.

Stories You May Have Missed:

  • Constraining Norms for Cyber Warfare Are Unlikely – GMU Biodefense PhD alum, Brian M. Mazanec, is talking to the Georgetown Journal of International Affairs about the realities of norms for cyber warfare. The question of whether constraining international norms for cyber warfare will emerge and thrive is of paramount importance to the unfolding age of cyber conflict. Some scholars think that great powers will inevitably cooperate and establish rules, norms, and standards for cyberspace. While it is true that increased competition may create incentives for cooperation on constraining norms, Mazanec argues that norm evolution theory for emerging-technology weapons leads one to conclude that constraining norms for cyber warfare will face many challenges and may never successfully emerge.
  • ABSA International Webinar- Behaving Safely in the Laboratory: Understanding Complexities of Building and Sustaining a Culture of Safety–  ABSA is hosting a 2-hour webinar session for three days. “The webinar will be offered Monday, April 3; Wednesday, April 5 and Friday, April 7, 2017.  Millions of dollars on engineering.  Thousands of dollars on PPE.  Hundreds of hours spent writing SOPs – and in one instant all of these controls can be negated with one inappropriate behavior.  Behavior is the bridge between written plans and desired outcomes.  But what does it take to behave safely?  Day 1 will focus on what it takes for an individual to behave safely – as behavior requires five critical items – and without these items – sustained behavior cannot occur. Day 2 will focus on motivating behavior – the differences between leadership and management – and the motivating factors which are extrinsic, systemic, and intrinsic. Day 3 will focus on building and sustaining a ONE SAFE culture – blending the efforts of the workforce, leadership, and safety officials.”
  • High Flu Activity Throughout the U.S. – The CDC has warned that the U.S. is still experiencing high flu activity in all regions. This flu season has seen elevated pediatric mortality, with six reported last week, bringing the total to forty pediatric deaths. “The CDC said there have been more hospitalizations and clinical visits for influenza-like illness (ILI) at this point in the flu season than in 2012-13, another season when H3N2 strain predominated. The CDC said the cumulative overall rate is 39.4 hospitalizations per 100,000 people. During the 2012-13 flu season, the rate was (38.2 per 100,000).”


Synthetic bio and dual-use anti-microbials

By Daniel McGown

Two articles were published in ACS Synthetic Biology this week, one from an MIT team and another from a team at Nanyang Technological University, iteratively outlining an approach for the custom design of a microbial hunter-killer against a pathogenic species.

In the first paper, Saurabh Gupta, Eran Bram, and Ron Weiss outlined proof of concept construction of an E. coli strain modified to do two novel things: 1) detect a quorum sensing signal emitted by Pseudomonas aeruginosa and 2) upon detection secrete a chimeric exotoxin designed to specifically destroy P. aeruginosa cells and nothing else. This use of passive detection to trigger an active and specific offense effectively converts the E. coli strain into a trap waiting for just P. aeruginosa – and because the toxin is secreted rather than requiring destruction of the cell, the trap can keep on trapping.

Matthew Wook Chang and company take a similar design and extend it two steps farther.   Firstly, they added a method to defeat one of P. aeruginosa’s best defenses, the biofilm.  Because P. aeruginosa biofilms include DNA into the extracellular matrix, they added a secreted DNAse to eliminate the DNA and disrupt the biofilm.  Secondly and perhaps more interestingly, the team retargeted the cell’s chemotaxis system by tying E. coli expression of a chemotaxis regulation protein to the presence of P. aeruginosa’s quorum sensing signal.  This caused the E. coli to gravitate toward P. aeruginosa and release their enzymatic arsenal where it would do the most P. aeruginosa damage.  With this latter addition, then, the waiting trap instead switched over to search and destroy.

This is a really cool idea – an appealing concept in a world that is running out of anti-microbials.  It brought to mind immediately the way the Russians used to use bacteriophages to attack bacterial infections, except these can be designed modularly to strike the right target instead of hoping nature is kind enough to deliver.  One has to wonder how easily it could be used in an infection inside a living system, but a proof of concept can’t be expected to jump that chasm – it’s cool enough that it works at all.  It will be nice, though, to see how readily the approach could actually be adapted to other pathogens and how well it will work clearing infections in vivo.

One also has to wonder, though, if the same idea couldn’t be turned in a different and less pleasant direction.  Could you use it to make a pathogen worse?  Say, could you build a pathogen that used the body’s chemokine and cytokine signals to specifically detect and defeat cells regulating immune responses with chimeric leukocidins or hemolysins or some such?  Beats me, but it feels like something of a goose and gander situation.

(image: Janice Haney Carr/CDC)
Daniel McGown is a first year PhD student in the Biodefense program with a background in molecular microbiology.