Pandora Report 3.17.2017

Happy Friday! In honor of  John Snow‘s birthday (the father of epidemiology), our featured image is the Broad Street pump map he used to combat cholera in the 19th century. Don’t miss out on the early registration discount for our biodefense summer workshop!

NAS Calls for Increased Federal Regulatory Agency Preparation for Growing Biotechnology Products 
The National Academies of Science (NAS) recent press release is emphasizing the need for federal regulatory agencies to prepare for greater quantities and ranges of biotechnology products. As the biotech world constantly evolves, regulatory agencies have struggled to keep up and this latest report states that in the next five to ten years, the pace will outmatch the U.S. regulatory system. According to the report, biotechnology, like CRISPR, has a rapidly growing scale and scope, which already stresses existing staff, expertise, and resources available at agencies like the EPA, FDA, and USDA. “To respond to the expected increase and diversity of products, the agencies should develop risk-analysis approaches tailored to the familiarity of products and the complexity of their uses, the report says. For biotechnology products that are similar to products already in use, established risk-analysis methods can be applied or modified, and a more expedited process could be used. For products that have less-familiar characteristics or more complex risk pathways, new risk-analysis methods may need to be developed.  Regulatory agencies should build their capacity to rapidly determine the type of risk-analysis approaches most appropriate for new products entering the regulatory system.” Within the report, NAS notes that the federal government needs to develop a strategy to combat the current issues and strengthen their ability to scan for future biotechnology products to better prioritize.

GMU Schar School Master’s Open House 
Have you ever wanted to study topics like CRISPR, bioterrorism, global health security, and pathogens of biological weapons? Good news – we’ve got just the program for you! Come check out GMU’s biodefense MS program at our Open House on Wednesday, March 22nd at our Arlington Campus, Founders Hall (Room 126) at 6:30pm. You can talk to some of our biodefense faculty and learn about our program. Whether you’re looking to take classes in person or earn a degree online, the biodefense MS is the best for the intersection of science and policy.

DARPA Works Towards “Soldier Cell” To Fight Bioweapons 
A bio-control system to fight off invading pathogens? Sounds like something out of a science fiction movie! Well, researchers at Johns Hopkins University just received funding from DARPA to develop the capacity to “deploy single-cell fighters” that would target and eliminate the lethality of certain pathogens. “‘Once you set up this bio-control system inside a cell, it has to do its job autonomously, sort of like a self-driving car,’ said Pablo A. Iglesias, principal investigator on the project. Iglesias, a professor of electrical and computer engineering in the Whiting School, shifted his research focus from man-made to biological control systems about 15 years ago. ‘Think about how the cruise control in your car senses your speed and accelerates or slows down to stay at the pace you’ve requested,’ Iglesias said. ‘In a similar way, the bio-control systems we’re developing must be able to sense where the pathogens are, move their cells toward the bacterial targets, and then engulf them to prevent infections among people who might otherwise be exposed to the harmful microbes’.” This angle, which is being focused on bacteria outside of the body, is just one potential tool in the biodefense arsenal.

Yellow Fever Outbreak in Brazil 
Since December of 2016, Brazilian health officials have reported an ongoing outbreak of yellow fever. The CDC has moved the alert to a  Level 2 – Practice Enhanced Precautions. A report recently published in the New England Journal of Medicine looks at the outbreak and the potential for cases in U.S. territories. In Brazil, there were 234 cases and 80 deaths reported between December and February. “Although it is highly unlikely that we will see yellow fever outbreaks in the continental United States, where mosquito density is low and risk of exposure is limited, it is possible that travel-related cases of yellow fever could occur, with brief periods of local transmission in warmer regions such as the Gulf Coast states, where A. aegypti mosquitoes are prevalent.”

GMU Biodefense Represented At Biothreats Conference
If you missed out on our coverage of ASM’s 2017 Biothreats conference, here’s a spotlight on GMU biodefense students attending this captivating three-day event. GMU’s biodefense program sent four graduate students to experience and report on the conference, which addressed biothreat research, policy, and response. “The program was exciting, according to the George Mason students in attendance. Mercer and Goble recall that the conference engaged topics of specific interest to them, their degree, and their futures. ‘I attended a panel that was very closely related to disease forecasting, my graduate thesis topic,’ Mercer said. ‘I was able to hear some of the cutting-edge research in that field, which was really helpful’. ‘I didn’t really have a part I didn’t like,’ Goble said. ‘I enjoyed the niche topics that were presented in both panel discussions and poster  sessions, from emergency operations to the FDA. All of these specific topics were extremely interesting to hear about and to know they are being researched’.”

Just How Well Did the 2009 Pandemic Flu Vaccine Strategy Work?
Researchers from the University of Nottingham recently looked at the success of vaccines in terms of preventing pandemic flu and reducing hospitalizations. Their work looked at the 2009 WHO-declared pandemic of the novel A(H1N1) virus, which infected around 61 million people around the world. Vaccines against the virus were rolled out globally between September and December of 2009, with the majority being inactivated A(H1N1)pdm09 influenza virus. Their work involved reviewing 38 studies between June 2011 and April 2016 regarding the effectiveness of the inactivated vaccine, which covered around 7.6 million people. “We found that the vaccines produced against the swine flu pandemic in 2009 were very effective in both preventing influenza infection and reducing the chances of hospital admission due to flu. This is all very encouraging in case we encounter a future pandemic, perhaps one that is more severe,” noted Professor Van Tam said. “Of course, we recognize that it took five to six months for pandemic vaccines to be ready in large quantities; this was a separate problem. However, if we can speed up vaccine production times, we would have a very effective strategy to reduce the impact of a future flu pandemic.” The 2009 pandemic A(H1N1) vaccine was 73% effective against laboratory confirmed cases and 61% against preventing hospitalizations. Interestingly, when looking at the vaccines’ effectiveness in different age groups, “they were shown to be less effective in adults over 18 years than in children, and effectiveness was lowest in adults over 50 years of age. Adjuvanted vaccines were found to be particularly more effective in children than in adults against laboratory confirmed illness (88 per cent in children versus 40 per cent in adults) and hospitalization (86 per cent in children versus 48 per cent in adults).”

Deadly Fungal Infection Arrives in U.S. 
While many are asking if surveillance methods for tracking the deadly CRE bacteria are adequate, a new issue is emerging in U.S. hospitals. Despite WHO’s recent plea for increased R&D surrounding certain resistant pathogens, it seems that more and more organisms of concern are springing up in U.S. hospitals. Since last summer, roughly three dozen people have been diagnosed with a highly resistant Candida auris infection. The fungal infection has caused worry ever since it was identified in 2009 due to its capacity as an emerging and resistant organism. Candida yeast infections are pretty common and known to cause urinary tract infections however, this strain is especially concerning because it easily causes bloodstream infections, has a stronger capacity for transmission between people, and is much more hardy in terms of living on skin and environmental surfaces. “Of the first seven cases that were reported to the CDC last fall, four patients had bloodstream infections and died during the weeks to months after the pathogen was identified. Officials said they couldn’t be sure whether the deaths were caused by the infection because all the individuals had other serious medical conditions. Five patients had the fungus initially isolated from blood, one from urine, and one from the ear.”

CDC Director Warns Loss of DHHS Funds Could Weaken Infectious Disease Prevention
Acting CDC director, Anne Schuchat, recently testified before Congress to make the case for for increased funding for several programs (one being the DHHS’s Prevention and Public Health Fund). Among other things, the Prevention and Public Health Fund is responsible for 12% of the CDC’s budget. Dr. Schucat’s testimony emphasized the previous usage of these funds in terms of vaccine delivery, disease surveillance, monitoring of water supplies, and tracking hospital-acquired infections. The growth of antibiotic resistance made her testimony and plea to Congress that much more relevant and urgent. “The CDC and other government agencies have in recent years cited the numerous public health threats posed by infectious diseases in general, and have lobbied officials for increased funding for research and development of novel vaccines and treatments as well as programs to effectively distribute interventions as needed. In 2016, for example, the CDC, DHHS, and National Institutes of Health requested federal funding to combat Zika, a request that was not approved until late in the year.”

Stories You May Have Missed:

  • Science on Screen – Don’t miss this great event hosted by Lawrence Livermore National Laboratory! On March 18th, you can watch the second installment of the Science on Screen series, featuring “Lawrence Livermore scientists Monica Borucki and Jonathan Allen, who will present ‘Reconstructing a Rabies Epidemic: Byte by Byte.’ This informative and entertaining lecture will explain how biologists and computer scientists used cutting-edge, ultra-deep sequencing technology to study the dynamics of a 2009 rabies outbreak. This case study, based on a dramatic increase (more than 350 percent) in the gray fox population infected with a rabies variant for which striped skunks serve as the reservoir hosts, will be used to help illustrate the changes in the viral genome during cross-species viral transmission. This lecture is appropriately paired with the feature-length film, “Contagion” (PG-13).”
  • Clorox Gets Spot on EPA A-Team – Clorox just earned its varsity spot on the team against hospitality-acquired infections. The EPA approved two of the company’s products in killing clostridium difficile spores. C-diff is a constant battle in healthcare facilities, so having the new tool in the infection prevention and environmental disinfection toolkit, is a huge advantage for many. “In addition, the cleaners and wipes recently become EPA-registered to disinfect against other bacterial infections, such as those caused by Staphylococcus epidermidis, Candida glabrata, and Enterococcus hirae. Moreover, the products are also effective against several viral pathogens, such as Middle East Respiratory Syndrome (MERS), and Severe Acute Respiratory Syndrome (SARS), measles, and Influenza A and B, among others.”

 

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).”

 

Pandora Report 3.3.2017

Welcome to March! On Tuesday, Russia cast its seventh veto and China cast its sixth veto to aid in protecting the Syrian government from UNSC actions and sanctions regarding chemical weapons attacks.

DIY Gene Editing Gets Faster, Cheaper, and More Worrisome
CRISPR/Cas-9 lab projects may not have been a possibility when I was in high school, but today’s students are getting a taste for genome editing. The technology has allowed relative amateurs to easily and cheaply learn gene editing tactics. “The question is, can we rely on individuals to conduct their experiments in an ethical and appropriately safe way?” says Maxwell Mehlman, a professor of law and bioethics at Case Western Reserve University, who is working with do-it-yourself scientists to develop DIY Crispr ethical guidelines. “The jury is out,” he says. “Crispr is too new. We have to wait and see.” GMU’s Dr. Koblentz has noted dual-use research is a wicked problem, and it seems that CRISPR/Cas-9 is one as well. Do-it-yourself (DIY) CRISPR kits can be purchased online for $150 and you can even get a handful of tutoring sessions for $400. While these products and experiments utilize harmless organisms, it’s not hard to see why so many are worried about the potential for misuse. Harvard University’s Dana Bateman visits high school classrooms for a lesson on CRISPR and during her time, she poses several ethical questions to the students. Dr. Bateman “asked a group of seventh-grade students whether Crispr should be deployed to bring extinct animals back to life. After a spirited discussion, one student asked, ‘How can we decide if we aren’t sure what will happen?’ Ms. Bateman replied that such questions will increasingly be part of public debate, and that everyone, including 12-year-olds, can benefit from learning about Crispr.” Learning the ins and outs of CRISPR isn’t so easy that it’s comparable to switching batteries in a remote, but probably closer to a complex set of IKEA instructions (ok, that’s a bit of an over simplification, but you catch my drift). Simply put, CRISPR does make DIY gene editing easier and cheaper, but foundational knowledge or instruction is still necessary. In this moment, we’re racing to catch up with the pace of innovation and understanding the risks versus rewards is proving more difficult. What are your thoughts on this hot topic?

China’s New BSL-4 Lab Plans 10729_lores
The Chinese mainland is hoping to see the construction of at least five BSL-4 labs by 2025. A laboratory in Wuhan is currently in the accreditation and clearance phase to work with the most deadly pathogens we face. While many celebrate the building  of this new lab, others are concerned about the biosafety and biosecurity risks. The increase in biodefense labs and programs has created several trade-offs for work with such high-risk pathogens.  Each new lab presents a new risk – for both biosafety failures and biosecurity failures. Biosafety failures are already plaguing U.S. labs – will this be the case with China’s labs? “The Wuhan lab cost 300 million yuan (US$44 million), and to allay safety concerns it was built far above the flood plain and with the capacity to withstand a magnitude-7 earthquake, although the area has no history of strong earthquakes. It will focus on the control of emerging diseases, store purified viruses and act as a World Health Organization ‘reference laboratory’ linked to similar labs around the world.” Skeptics have pointed to several escapes of SARS from a high-level containment facility in Beijing. Several biosafety and biosecurity experts are highlighting the need for transparency and an open and responsible culture. Addressing issues with staff at all levels and opening the floor for an honest and frank discussion regarding concerns from those working in the environment is vital to addressing the issues that may not be seen at a higher level.

WHO’s List of Superbug Super Offenders  screen-shot-2017-02-28-at-10-19-28-am
If there was an A-list for multi-drug resistant organisms, this would be it. This first-of-its-kind list, highlights the “priority pathogens” that comprise of twelve families of bacteria “that pose the greatest threat to human health”. “The list was developed in collaboration with the Division of Infectious Diseases at the University of Tübingen, Germany, using a multi-criteria decision analysis technique vetted by a group of international experts. The criteria for selecting pathogens on the list were: how deadly the infections they cause are; whether their treatment requires long hospital stays; how frequently they are resistant to existing antibiotics when people in communities catch them; how easily they spread between animals, from animals to humans, and from person to person; whether they can be prevented (e.g. through good hygiene and vaccination); how many treatment options remain; and whether new antibiotics to treat them are already in the R&D pipeline.” Not only is the publishing of this list an indicator as to the seriousness of the issue, but it signals a desperate plea for the pharmaceutical industry to develop new antibiotics. The three most critical bacteria on the list are carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, and Enterobacteriaceae that are both carbapenem-resistant and ESBL-producing.

Kim Jong Un and the Case of the of VX Nerve Agent 
Last week saw the shocking revelation by Malaysian police that Kim Jon-nam, half-brother to North Korea’s Kim Jong-un, had been assassinated with the nerve agent, VX. The use of VX has left many wondering gif Kim Jong-un decided to use this overt form of assignation to signal his possession and willingness to use it or was this a botched assassination that was supposed to look like a natural death? Since this event has taken us into uncharted territory, many chemical and biological weapons experts are weighing in on what this means. GMU biodefense professor and graduate program director, Gregory Koblentz, pointed out that “it’s very hard to make an accurate intelligence assessment”. The dual-use nature of bio-chem weapon production facilities and materials makes intelligence gathering that much more difficult. “While Kim Jong-un is unpredictable, seasoned Korea watchers see method in what may sometimes seem like madness. And that leads them to doubt that he actually intends to use nuclear weapons — which make more sense as a bargaining chip in dealing with the US and other powers. Pyongyang’s chemical arsenal is a different prospect, however. ‘If there’s a conflict on the Korean peninsula, North Korea would probably use chemical weapons early on,’ Koblentz said.”

PHEMCE Review: Accomplishments and Future Areas of Opportunity 
GMU Biodefense PhD student and VP of Marketing at Emergent BioSolutions, Rebecca Fish, is looking at the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) and their recent strategic implementation plan. Highlighting their four goals and sample accomplishments, Rebecca looks at their work on emerging infectious diseases (EIDs) like Ebola response and Zika. While PHEMCE has made great progress, there is still room for engagement and opportunity. Rebecca points to their plans to incentivize innovation, “while biotechnology is increasing at an exponential rate, and the opportunity for misuse (bioterrorism) is increasing, the number of companies interested in making significant investment in medical countermeasures development is decreasing. There are important MCM innovation gaps that need to be addressed.” She notes that PHEMCE activity encompasses a great deal of federal agencies, which can make work that much more challenging. “However, the PHEMCE effort still requires strong, centralized leadership and a comprehensive strategic plan with measurable outcomes against which progress can be reported. It’s impressive that so many groups are working on these challenges, but who is determining the overall strategic plan? How does it come together? Which single individual has responsibility for the entire biodefense strategic effort? Who is managing the enterprise U.S. biodefense budget? No one. No one has clear accountability for the U.S. biodefense strategy, and this puts our country at risk.”

Johns Hopkins Center for Health Security Announces 2017 Emerging Leaders in Biosecurity
The Center for Health Security at Johns Hopkins University has announced the new class of emerging leaders in biosecurity. GMU is happy to announced that one of our Biodefense PhD students, Saskia Popescu, was named among the 2017 emerging leaders. “The program’s goal is to build a multidisciplinary network of biosecurity practitioners and scholars. ELBI is supported by a grant from the Open Philanthropy Project. As part of its commitment to grow and support the field of biosecurity, the Center has selected 28 Fellows from the US, the UK, and Canada. As in previous years, this year’s Fellows have backgrounds in government, the biological sciences, medicine, national security, law enforcement, public health preparedness, and the private sector.” Congrats to the new class of emerging leaders!

Multivariate Analysis of Radiation Responsive Proteins to Predict Radiation Exposure in Total-Body Irradiation and Partial-Body Irradiation Models
GMU Biodefense PhD student, Mary Sproull, is working to strengthen medical countermeasures in the event of a radiological or nuclear attack. Advanced screening and medical management of those exposed are vital during such an event. “In such a scenario, minimally invasive biomarkers that can accurately quantify radiation exposure would be useful for triage management by first responders. In this murine study, we evaluated the efficacy of a novel combination of radiation responsive proteins, Flt3 ligand (FL), serum amyloid A (SAA), matrix metalloproteinase 9 (MMP9), fibrinogen beta (FGB) and pentraxin 3 (PTX3) to predict the received dose after whole- or partial-body irradiation.” Researchers found that the novel combination of radiation responsive biomarker proteins are an efficient and accurate tactic for predicting radiation exposure. You can read the paper here.

Stories You May Have Missed:

  • OPCW Call for Nominations For A Workshop on Policy & Diplomacy for Scientists – The OPCW Technical Secretariat is organizing a workshop, “Introduction to Responsible Research Practices in Chemical and Biochemical Sciences”, from September 12-15, 2017. “The objective of the workshop is to raise awareness among young scientists on the policy and diplomacy aspects that are related to the use of chemicals in various scientific disciplines, including chemistry, biochemistry, biotechnology, and other related fields.” Check out their link for more info on applying for admission and/or a scholarship.
  • Epidemic Tracking Tool Wins Open Science Grand Prize – A new prototype, Nextstrain, has won the new Open Science Prize. This tool analyzes and tracks genetic mutations during the Ebola and Zika outbreaks and they’re hoping to use it for other viruses. “Everyone is doing sequencing, but most people aren’t able to analyze their sequences as well or as quickly as they might want to,” Bedford said. “We’re trying to fill in this gap so that the World Health Organization or the U.S. Centers for Disease Control and Prevention — or whoever — can have better analysis tools to do what they do. We’re hoping that will get our software in the hands of a lot of people.”

Pandora Report 2.24.2017

Happy Friday and welcome to your weekly dose of all things biodefense! A preliminary report from the Malaysian police has found that VX nerve agent was most likely used to murder Kim Jong-nam.

Summer Workshop on Pandemics, Bioterrorism, and Global Health Security: From Anthrax to Zika 
Want to dabble in the world of global health security? Don’t miss out on 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!

Progress Report on BARDA & Project Bioshield 
A 10-year report card was recently published for these two efforts to defend the U.S. against biological threats. The report found 80 candidate countermeasures, 21 stockpiled countermeasures, and 6 FDA approvals supported by BARDA and Project Bioshield. “Over a decade has passed since the anthrax attacks of 2001; preparedness has increased substantially since that time, and defense against CBRN threats has become melded into national security. Both BARDA and Project Bioshield are essential elements of national security, and, especially in light of a change in presidential administration, it is important to emphasize the critical role these agencies have had in fortifying the nation against intentional CBRN threats. Larsen and Disbrow note, however, that despite the reauthorization of Project Bioshield in 2013 with annual funding at $2.8 billion (from 2014-2018), that funding is subject to annual congressional appropriations; as such, only a fraction of that funding has been appropriated.”

BWC Newsletter 
If you’re looking to keep tabs on the Biological Weapons Convention, we’ve got just the place for you. The BWC Implementation Support Unit has prepared a newsletter to better support communication among States Parties and encourage involvement in BWC-related issues and events. The first issue discusses the recent Eighth Review Conference and news like the launch of EU projects to support BWC universalization and a Confidence-Building Measures reminder letter (deadline for submission is April 15th!).

screen-shot-2017-02-21-at-2-11-26-pmCDC Lab Closure Due to Safety Concerns
The CDC has temporarily closed down its Biosafety Level-4 laboratories following the finding that their air supply hoses to researchers in protective suits were not approved for use. “‘We have no evidence that anybody has suffered ill health effects from breathing air that came through these hoses,’ Stephan Monroe, associate director for laboratory science and safety at the CDC, told Reuters. Monroe said he was confident scientists were not exposed to pathogens because the air they breathed passed through HEPA filters. The suits they wear also use positive air pressure to prevent pathogens from entering the suit.” Safety tests are currently being performed while employees are being notified and monitored. Interestingly, Monroe’s position is a newly minted one, having been established in 2015 to combat the continuous findings of major lab safety failures involving anthrax, avian influenza, and Ebola in CDC labs.

Why Bill Gates Worries About Biological Threats
Bill Gates recently spoke to Business Insider following his speech for the Munich Security Conference, in which he highlighted his real concerns for global health security. He noted that conflict areas and regions that are struggling to find stability are perhaps the most challenging in terms of outbreak containment. Gates emphasized the vulnerability for genome editing of a virus to make it more contagious, and also the advances in biotechnology that may help prevent the spread of an epidemic. “The point is, we ignore the link between health security and international security at our peril. Whether it occurs by a quirk of nature or at the hand of a terrorist, epidemiologists say a fast-moving airborne pathogen could kill more than 30 million people in less than a year. And they say there is a reasonable probability the world will experience such an outbreak in the next 10-15 years.” Perhaps the most important thing on our “to-do” list is to invest in vaccines, drugs, and diagnostics. We have a tendency to put these priorities lower on the totem pole until a major public health crises occurs however, Gates highlights their relevance. The launch of the new Coalition for Epidemic Preparedness Innovations (CEPI) is one step closer to bridging this gap. “The really big breakthrough potential is in emerging technology platforms that leverage recent advances in genomics to dramatically reduce the time needed to develop vaccines. Basically, they create a delivery vehicle for synthetic genetic material that instructs your cells to make a vaccine inside your own body.” Gates also emphasized the importance of strengthening basic public health systems, especially in vulnerable countries – adding to that age old saying, “an outbreak anywhere is an outbreak everywhere”.

screen-shot-2017-02-23-at-7-48-50-amFinancing Pandemic Preparedness At the National Level = First Line of Defense
Pandemic preparedness funding is one of those common sense investments…right? Unfortunately, many don’t always make it a priority. Ebola alone cost billions, including a $2.27 billion allocation for response by the U.S. government. Dozens of after-action reports and papers on lessons learned have been published since the outbreak. Peter Sands noted that “all these reviews – including the one I chaired  for the US National Academy of Medicine – agreed on three key priorities: strengthening preparedness at a national level; improving coordination and capabilities at a regional and global level; and accelerating R&D in this arena.  Over the last twelve months progress has been made in implementing many of these recommendations, but big gaps and weaknesses remain. As a recent paper in the British Medical Journal put it, there has been ‘ample analysis, inadequate action’.” The highest priority though is preparedness at a national level. The International Working Group on Financing Pandemic Preparedness was created in 2016 as a means to propose ways in which national governments and partners can work to establish sustainable financing to strengthen their pandemic preparedness. Their focus “includes domestic resource mobilization, development assistance and private sector engagement. For many countries, financing preparedness through the domestic public sector budget is the best way to ensure sustained funding and seamless integration with the rest of the health system. This requires ensuring sufficient priority is attached to investing in pandemic preparedness in budget allocations. In some countries, there may also be scope to increase the fiscal envelope through improvements in tax design and collection or even hypothecated taxes.”

Insider Threats 
Get ready to add this new book to your reading list. Matthew Bunn and Scott D Sagan are looking at insider threats like nuclear material theft and Edward Snowden. “Insider Threats offers detailed case studies of insider disasters across a range of different types of institutions, from biological research laboratories, to nuclear power plants, to  the U.S. Army.” Don’t miss the chapter from Jessica Stern and Ronald Schouten, “Lessons Learned from the Anthrax Letters”. Stern and Schouten look at the investigation of the Amerithrax attacks and provide a portrait of Ivins and his troubling behavior. They also address “the combination of regulatory changes, red flags missed by Ivins’s colleagues, and the organizational and cognitive biases that contributed to the failure to identify Ivins as a potential insider”, and the current environment and new regulations.

Stories You May Have Missed:

  • Former Secretary of Defense Outlines the Future of Warfare – “Two years ago, Barack Obama appointed a new Secretary of Defense, Ashton Carter—a technocrat physicist, an arms control veteran, and a professor at Stanford—to help close this divide.” Carter recently sat down with WIRED magazine and discussed the challenges facing the White House. When asked about the impact of autonomy on warfare, Carter notes that it will change it in a fundamental way, but also points biotechnology. “I think if there is going to be something ever that rivals nuclear weapons in terms of the pure fearsomeness of their destructiveness it’s more likely to come from biotechnology than any other technology. Looking back decades from now, I do think the biological revelation could rival the atomic revolution for the fearsomeness of the potential. I think that’s one reason we need to invest in it. And although biotechnology has not been a traditional area for Defense, the new bridges that they build shold not only be to the IT tech community but also to the biotech communities in the Valley.”
  • Did Salmonella Take Down the Aztecs?– History and infectious disease? That’s surely the best way to start a weekend! Researchers recently looked at the DNA of a 500-year-old bacteria to study one of the worst epidemics in history. “In one study, researchers say they have recovered DNA of the stomach bacterium from burials in Mexico linked to a 1540s epidemic that killed up to 80% of the country’s native inhabitants. The team reports its findings in a preprint posted on the bioRxiv server on 8 February. In 1519, when forces led by Spanish conquistador Hernando Cortés arrived in Mexico, the native population was estimated at about 25 million. A century later, after a Spanish victory and a series of epidemics, numbers had plunged to around 1 million.” After extracting and sequencing the DNA from the teeth of 29 buried people buried in the highlands of southern Mexico, all but five were found to be linked to cocoliztli. “Further sequencing of short, damaged DNA fragments from the remains allowed the team to reconstruct two genomes of a Salmonella enterica strain known as Paratyphi C. Today, this bacterium causes enteric fever, a typhus-like illness, that occurs mostly in developing countries. If left untreated, it kills 10–15% of infected people.”

Pandora Report 2.17.2017

screen-shot-2017-02-15-at-10-06-56-amHappy Friday! Since Tuesday was Valentine’s day, it was fitting to have a super romantic story about Ebola super-spreaders and their role in causing most of the cases. Have you ever wondered why killer viruses are on the rise or what some of these infectious disease terms mean?

ASM Biothreats 2017 Highlights 
If you missed this event or weren’t able to make some of the sessions, check out our overview! GMU sent four graduate biodefense students to ASM’s biothreats conference to not only aid in their education, but also to report back for our readers. With their unique backgrounds, we’ve got articles on the FDA’s Animal Rule, international biosecurity efforts, and more. Check out the link above and you’ll find a special edition post with all of our highlights.

A Step Closer Towards Human Embryo Editing
A new report from an international committee put together by the U.S. National Academy of Science and the National Academy of Medicine found that a clinical trial regarding DNA editing of a human embryo “might be permitted, but only following much more research” on risks and benefits, and “only for compelling reasons and under strict oversight.” Consideration would be given to couples who are both afflicted with serious genetic disease and editing is “really the last reasonable option” for them to have a healthy child. While some applaud this as a first step towards a very specific and narrow subset of DNA altering, “others see the report as lowering the bar for such experiments because it does not explicitly say they should be prohibited for now. ‘It changes the tone to an affirmative position in the absence of the broad public debate this report calls for,’ says Edward Lanphier, chairman of the DNA editing company Sangamo Therapeutics in Richmond, California.” You can read the full report here.

The Biotechnological Wild West: the Good, the Bad, and the Underknown of Synthetic Biology
GMU Biodefense PhD student and Predoc at Lawrence Livermore National Laboratory, Yong-Bee Lim, is taking on the 2017 ASM Biothreats conference and the pipette-slinging world of synthetic biology. Lim first focuses on the panel at ASM’s conference, which looked at the current state of synbio and where the future might take us. Like most things in life, there’s also a flip side to that coin – the negative aspects of this new technology. “While the benefits derived from synthetic biology are great, presenters noted that it suffers from the dual-use dilemma: the same information applied to beneficial uses could also be repurposed for nefarious purposes. Dr. Hassell noted that synthetic biology increases biologically-derived risks through three mechanisms. First, synthetic biology can be used to enhance existing microbial threats; synthetic biology allows actors to more easily manipulate the characteristics of microbes, including increasing environmental stability and introducing hypervirulence. Secondly, traditional methods of restricting access to biological select agents and toxins (BSATs) may be less effective in an age where synthetic biology can be used to construct microbes de novo. Finally, synthetic biology can be used to construct novel threats that are meant to subvert countermeasures.” Lastly, one of the most interesting components to this presentation and Lim’s article is the underknown components to synethic biology. The erosion of the knowledge and technical barriers and the rise of the do-it-yourself (DIY) practitioners all give way to a new frontier in terms of benefits and dangers.

Broad Institute Wins CRISPR Patent 
This week, the U.S. Patent Office appeal board ruled that the dispute regarding the discoveries between the University of California, Berkeley and the Broad Institute do not overlap. “The ruling is a win for the Broad Institute, which had asked for the finding of no interference. It will be able to retain its valuable patents, which cover the use of CRISPR in human and animal cells. In a statement, Berkeley said it “respects” the decision but still maintains that Berkeley biochemist Jennifer Doudna and European collaborator Emmanuel Charpentier were the first to invent the CRISPR system.” The CRISPR patent dispute has brought to light the most foundational question of who truly owns the patent rights to CRISPR work in animals and plants. This new development doesn’t mark the end of the CRISPR dispute, as many expect Berkeley to appeal the decision and the Broad Institute’s patent is facing dispute from other researchers, including the Rockefeller University. While the CRISPR patent road may have been smoothed for a bit, it will continue to remain rocky and cause ripples for business developments and the biotech industry.

Defense Civil Support: DoD, HHS, and DHS Should Use Existing Coordination Mechanisms to Improve Their Pandemic Preparedness screen-shot-2017-02-14-at-10-41-11-am
In this Government Accountability Office (GAO) report, they found that the DoD should utilize guidance developed to aid in support of civil authorities (specifically HHS and DHS). “HHS and DHS have plans to guide their response to a pandemic, but their plans do not explain how they would respond in a resource-constrained environment in which capabilities like those provided by DOD are limited. DOD coordinates with the agencies, but existing coordination mechanisms among HHS, DHS, and DOD could be used to improve preparedness. HHS’s Pandemic Influenza Plan is the departmental blueprint for its preparedness and response to an influenza pandemic.” The GAO’s goal was to assess the DoD’s plans and processes to support civil authorities during a pandemic, of which they found that the existing coordination mechanisms should be used to explore opportunities to improve preparedness if their capabilities are limited.

Global Health Security Transparency 
Global health security is a finicky creature as it requires cooperation and transparency from all countries. One weak link in the chain can cause an international public health crisis. No More Epidemics is imploring countries to publish their Joint External Evaluations (JEE) performed by the GHSA (Global Health Security Agenda). As of now, only Ethiopia, Liberia, Peru, Uganda, UK, and the U.S. have openly shared their JEE’s. “Knowledge of baseline data provided by the JEE will result in more effective programming, prevention and detection of infectious disease outbreaks and early response. The JEE and roadmap processes are critical tools for civil society to use in developing appropriate and adequate programming to help countries close health systems gaps and become IHR-compliant. Transparency and accountability are vital in addressing global health threats. No More Epidemics urges all countries carrying out their Joint External Evaluations to make the results publicly available and for these to be made available on the World Health Organization’s Strategic Partnership Portal, the online repository for tracking funding, donor profiles and country level data.” Information sharing is also a mechanism for strengthening partnerships among countries.

Webinar on Ebola’s Aftermath 
Doctors Without Borders (MSF) will be hosting this live webinar on Thursday, February 23rd at 8pm EST. Following the publication of the book, The Politics of Fear: Médecins Sans Frontières and the West African Ebola Epidemic, the MSF webinar will do a deep-dive into the 2014/2015 outbreak and the lessons learned. This event will include a panel of MSF experts, who were directly involved in the MSF response in West Africa.

Fighting Antimicrobial Resistance with Physics
The battle against antimicrobial resistance (AMR) isn’t slowing and the proposed strategies emphasize the need for increased research and development of new antimicrobial agents, which means we’re running out of options. Swinburne University is trying a new tactic though – physics. “Elena Ivanova was studying physical surfaces that could repel bacteria before they even had time to settle. In clinical settings, such as hospitals and dental practices, 80% of infections are caused by bacteria that cling to surfaces in such densities that no antibiotic can remove them. First, she tried making surfaces so smooth that bacteria would, theoretically, simply slide off. Although that was the case for some bacteria, many others—such as the common Staphococcus aureus, or staphstill managed to cling on and multiply.” This is where Greg and Jolanta Watson come in – they have amassed a huge collection of biological samples in their laboratory. Ivanova and the Watsons communicated back and forth regarding natural properties that might make bacteria incapable of sticking to and growing on surfaces. Starting with cicada wings, Ivanova found that it was able to kill one of the two main types of bacteria, which was a partial success. Next, a gecko’s skin was tested, which revealed a wealth of knowledge. “Green had added a sample of the small, rod-shaped bacterium that causes gingivitis, Porphyromonas gingivalis, to the surface. In total, he added around 10 million microbes every day for a week. What’s more, this mass of microbes was given everything that they needed for a good life: a constant temperature of 98.6˚ F, an atmosphere without oxygen, and a daily ration of food. Regardless, after the week, nearly all were punctured and torn, their cellular carcasses strewn over the gecko skin. ‘Bacteria are trying to move and settle on the surface,’ Green says. ‘And they’re just getting spiked and skewered by these long hairs’.” Looking to nature, these researchers have focused on the physics of repelling bacterial growth, which may help broaden the arsenal against resistant germs.

Stories You May Have Missed: 

  • Talking About Bioethics & Policy in the U.S. Under the Trump Administration – Dual-use research of concern, CDC’s new quarantine rule, and the Animal Rule are all topics involving bioethics and Johns Hopkins University is hoping to provide the resources needed to address these complex issues. The new administration brings with it concerns over vaccine skepticism and how they will handle these bioethical dilemmas. How will Trump address the work of biotechnology and public health crises?
  • Breaking Barriers: Women in Science Event: Don’t miss this March 8th event at 6pm at Top of the Town in Arlington, VA. The 3rd annual reception will “bring together scientific, political, and cultural leaders to celebrate the achievements of women in STEM and take a stand for the critical role women play in science and technology communities”.
  • The Cost of Biosecurity – For $1 million a year, you can buy yourself global biosecurity! A recently published list of the unit staff costs from the 2017 BWC Meeting of State Parties, gives an eye-opening revelation into the cost of biodefense. For $1.1 million a year, you can financially support the implementation unit staff of the BWC – quite a bargain, no?
  • Surprise Us, Mr. Trump – A Letter From the Global Health Community – In this editorial article from The Lancet Global Health, the authors point to the role of the U.S. in the WHO Executive Board and the future of WHO leadership. “Two legislative bills introduced in early January in the US House of Representatives and Senate are seeking to withhold funds from the UN and open a way for the USA to leave the global body, and therefore withdraw membership of WHO.” The current political and global health atmosphere is unsettled, which has many concerned about the future of U.S. involvement in global health programs.
  • CRISPR Creates TB-Resistant Cattle – Chinese researchers have created tuberculosis resistance in cattle using CRISPR/Cas9. “As the researchers reported today in Genome Biology, they used somatic nuclear transfer to get the edit into an egg cell, creating 11 cows in vitro with NRAMP1 (nine using Cas9 nickase) and demonstrating that the gene provided increased resistance to tuberculosis.Moreover, they said that while the Cas9 nickase did not completely eliminate off-target edits, it did reduce them, especially when compared to standard Cas9 which creates double-strand breaks and is much more likely to create indel mutations via the non-homologous end-joining DNA repair pathway.”

ASM Biothreats 2017

screen-shot-2017-02-15-at-9-40-26-amGMU Biodefense sent four graduate students to give you a “boots-on-the-ground” viewpoint for the 2017 ASM Biothreats conference. In our special edition post we have a full range of coverage for this three-day conference on biological threats and safety.

Zach Goble is looking at international collaboration against biological threats and the importance of recognizing foreign organizations for their help in aiding research endeavors. Next, he looks to the symposium on national bioterrorism emergency response. Pointing to the work done by different states and the proposed model by David Ladd, he emphasizes that these are definite steps in the right direction, but will need continued work.

Greg Mercer reviews the panel session “Predicting Emergence by Understanding the Past: Methods that Move Us Towards Predictive Biology“. In his overview of this panel on efforts to get ahead of the evolutionary curve, Greg discusses each speaker and their contributions to the field, as well as where they think the future will take us.

Stephen B. Taylor covers Dr. Fauci’s talk on pandemic preparedness and his experience throughout the years. In this overview, Dr. Fauci points to the unique challenges that followed each health crisis and how certain administrations responded. Stephen also takes us through the melioidosis panel regarding this neglected tropical disease. He notes the high cost of treatment and the inability for most endemic countries to support response and prevention efforts.

HyunJung (Henry) Kim– takes us on a journey through the FDA Animal Rule and its path to success. Henry uses this plenary sessions to discuss the PEP, PrEP, and Passive Transfer aspects of animal modeling.

Predicting Emergence by Understanding the Past: Methods that Move Us towards Predictive Biology

By Greg Mercer

I attended ASM BioThreats 2017’s panel “Predicting Emergence by Understanding the Past: Methods that Move Us towards Predictive Biology,” where a panel of researchers presented their recent efforts to get ahead of the evolutionary curve and anticipate new developments in infectious disease.

Marco Vignuzzi, of the Pasteur Institute, described his efforts to monitor, predict, and target RNA virus evolution. RNA viruses mutate constantly; any response to them must into account incremental changes and variations. Vignuzzi described a large population of many low-frequency mutants as a quasi-species or “cloud.” One can sequence the average genetic profile of this cloud, known as the “consensus sequence.” This population exists across a fitness landscape, ranging from well-adapted to poorly-adapted. The natural evolutionary tendency of a fast-mutating RNA virus is to “climb” this landscape to the highest possible fitness—this is the most successful disease. But Vignuzzi suggests that a virus could be artificially altered to undergo exactly the wrong mutations, making it less fit and causing it to die off. Exactly how to do this remains a mystery, but it’s an exciting possibility.

Barbara Han, of the Cary Institute of Ecosystem Studies, presented her research on machine learning for forecasting zoonotic disease. Han takes a macro-ecological approach to disease, focusing on hosts. Factors like biodiversity and population density affect disease rates, so understanding zoonotic diseases means collecting a great deal of information about the animals that carry them. This information tends to be collected based on specific concerns about animal reservoirs; Han noted that since bats are a suspected reservoir for Ebola and other diseases, there’s been a massive surge in surveillance. It turns out, though, that they carry fewer zoonoses than we might expect. Right now, Han is studying bats to try to identify instances where viruses might spill back into bat reservoirs from human populations, making outbreaks harder to stop. She is also working with data about the health of rodent populations, with the hypothesis that lower biodiversity in a particular area will put humans at a higher risk for a spillover.

David O’Connor, from the University of Wisconsin-Madison, is looking at viruses that aren’t on the radar yet, though maybe they should be. O’Connor examines animal species to find traits that make spillover events likely. Specifically, he presented the theory that simian arteriviruses might be to blame for the mysterious simian hemorrhagic fever. There’s not enough information to know for sure without another outbreak, but O’Connor argues that there is enough information at our disposal to begin to make predictions “to the left of the surveillance curve,” and target surveillance at diseases that aren’t yet a top threat, but could emerge as one.

Melioidosis: Uncovering a Neglected Tropical Disease

By Stephen Taylor

The ASM Biothreats Melioidosis Panel on Tuesday, February 7th, shed light on a largely ignored infectious disease that runs rampant in developing Southeast Asian countries. The speakers, Dr. Direk Limmathurotsakul, the Head of Microbiology at Mahidol-Oxford Tropic Medicine Research Unit, and Dr. Frances Daily, of Diagnostic Microbiology Development Programme, brought a wealth of first-hand knowledge and experience diagnosing and treating this disease in Thailand and Cambodia.

Melioidosis is an infection caused by Burkholderia pseudomallei, a bacterium often found in soil and water.  It is known to cause fever, arthritis, and abscesses of vital organs.  Once inoculated with bacteria, carriers typically experience an incubation period between 1 and 21 days before melioidosis symptoms appear.  Humans acquire B. pseudomallei by inhaling contaminated dust, ingesting contaminated water, or coming into contact with contaminated soil.

In the United States, B. pseudomallei is classified by Health and Human Services and the U.S. Department of Agriculture as a Tier 1 Select Agent, meaning it poses a significant threat to human and animal health and safety and presents a great potential for deliberate misuse.  The Soviet Union and the United States are both believed to have studied B. pseudomallei as a potential biological warfare agent in the 1940s.

In his extensive work caring for patients in northeast Thailand, Dr. Limmathurotsakul documents numerous cases of melioidosis on an annual basis, many of them fatal.  Thailand’s Bureau of Epidemiology, however, only documents about 12 melioidosis deaths per year.  Dr. Limmathurotsakul chalks up the disparity to a poor public health surveillance apparatus and cultural barriers in reporting.  Public health laboratories in Thailand are poorly equipped for diagnostics. Furthermore, physicians in Thailand are not well trained to utilize laboratory diagnoses, nor are they well versed in the transmission and symptoms of melioidosis.  When local health professionals do detect outbreaks of the disease, they are hesitant to report them to the Bureau of Epidemiology for fear of being stigmatized as the only locale to have a significant melioidosis outbreak.

Dr. Daily has encountered similar problems working in Cambodia.  Due to climate change, the rainy season in Cambodia lasts longer every year and with it, the number of melioidosis outbreaks detected by her team also grows.  The Cambodian government, however, is unable to respond effectively to these outbreaks due to a lack of diagnostic capability, patient data, and funding.  Treatment for the infection, which averages a cost of 65 USD, is expensive compared to the Cambodian per capita income of just over 1,100 USD.  Many families struggle to pay for treatment, often going into debt or selling property to afford it.

What can be done to improve detection and treatment of melioidosis?  All of the panel members recommended improving the education and training of the public health and medical workforce.  Knowledge of melioidosis needs to be integrated into training for public health workers in laboratory diagnosis.  Protocols for diagnosis and treatment of melioidosis should be incorporated into medical school curricula.  The speakers also expressed hopes that Thailand and Cambodia would be able to build their capacity to detect and report infectious diseases. Combining his limited data on melioidosis with predictive modeling algorithms, Dr. Limmathurotsakul has estimated that there are 165,000 cases of melioidosis worldwide each year, 89,000 of which result in death.  He hopes the estimates will spur melioidosis researchers worldwide to compile confirmed-case data and paint a more accurate picture.  Then national and international policymakers will have better information to support clinicians and public health officials in their local efforts to fight the disease.

Licensure under the FDA Animal Rule: A Path to Success

By HyunJung (Henry) Kim

Michael Merchlinsky, a subject matter expert from BARDA/CBRN, was the first speaker in this ASM Biothreats 2017 plenary session, overviewing history of the Animal Rule in the US. The Animal Rule is well-known as an innovative policy forming the foundation of U.S. biodefense policies. When no alternatives are available, the Animal Rule provides an investigational mechanism for figuring out “predictive” responses from new medical countermeasures (MCMs) relevant to calculating a dose in humans. Under the Animal Rule, licensure is a legal status awarded by FDA that assures the public that studies to demonstrate safety and efficacy have been performed. According to Merchlinsky’s presentation, it is worthy to note that the Animal Rule was born in the basis of national security purposes, increasingly apparent from Gulf War to 9/11. The primary purpose of the Animal Rule is to increase preparedness and provide means to confidently respond to a public health emergency. Based on the national security perspective at the state-level, Michael Merchlinsky reviews the pros and cons of the Animal Rule. He notes that the Animal Rule is the best course of action for assuring ‘safety’ and ‘efficacy’ where no other alternative is available. Moreover, MCMs under the Animal Rule can attain pre-EUA status during developmental path-MCMs saved in the Strategic National Stockpile (SNS). On the other hand, a critical limitation is that the Animal Rule is inherently longer, harder, and less predictive than traditional pathways.

Next, Dr. Mario Skiadopoulos and Christine Hall represented Emergent BioSolutions and spoke to the regulatory pathway for anthrax and botulism medical countermeasures. BioSolutions applies animal models based on the subject of rabbits as well as non-human primate (NHP) to develop vaccines against anthrax and botulism. It was very interesting to know that there are three types of experiments in animal modeling; Post-Exposure Prophylaxis (PEP), Pre-Exposure Prophylaxis (PrEP) and Passive Transfer. The PEP type demonstrates added value of vaccine over antibiotics alone, in post-exposure settings, whereas the PrEP type established correlation between pre-challenge TNA tilter and probability of survival. The Passive Transfer type demonstrates that neutralizing antibody alone is capable of protection. Compared with the speaker from government sector, speakers from the private sector point to more practical challenges that field researchers are facing under the Animal Rule. They argue that there is no regulatory precedent for licensing a vaccine under the Animal Rule. Technically speaking, it is not clear which time points or which kind of animal models can bridge animal-to-human data. For instance, we have never known which animal model is akin to human trials between rabbits and NHP, as well as which time point is appropriate to apply to humans among the 80%, 90% or 100% survival points from the result of animal models. Consequently, the Animal Rule is essential not only in MCMs development and the realm of national security, but also carries with it many challenges both in government and private sectors. Overall, the inclusion of both government and private sector viewpoints presented the full spectrum of the Animal Rule and its complexities regarding MCM development.

Should I Stay or Should I Go? National Bioterror Emergency Response Preparedness

By Zach Goble

The theme of this ASM Biothreats 2017 symposia was perhaps one of the more noteworthy callings for collaboration among groups. With more than 17 years of experience as the director of Hazardous Materials Emergency Response at the Massachusetts Department of Fire, David Ladd emphasized the need for a unified response when encountering any number of hazards. His slogan during his dialog, “what happens on the left coast, then happens on the right coast”, stressed the importance of initiating and maintaining communication with organizations near and far. No one stays unaffected in the world of today and without the exchange of ideas, experiences, and procedures disasters can have an overwhelming effect.

Rich Ozanich, from Pacific Northwest National Laboratory and Christina Egan, from the NY Dept. of Health, both echoed that close collaboration is a key factor in response. While Rich laid out the Department of Homeland Security’s framework for “The Onion”, which is a set of procedures to guide first responders in the event of a biothreat incident. The emphasis here was that to be successful the training for such events needs to be coordinated at a local, state, and national level.  Christina detailed the many training programs tailored to biological threat response within Emergency Management Departments specific to various states such as Minnesota and Wisconsin. The message here was that while many great programs exist at the state level, there is not a unified national response to confront CBRN threats with the United States.

David Ladd concluded the panel by presenting a proposed model for National Bioterrorism Response that was submitted by the Interagency Board in January, 2017. In the absence of a nationally recognized system for protecting the nation against bioterrorism, the need for such a system is certainly justified. This document provides a model for bringing together various organizations and departments to create a network of local bioterrorism response teams ready to deploy when the need arises. Models such as these represent steps in the right direction to achieving a unified response in ensuring the public remains safe from biological threats.