Pandora Report 6.9.2017

Hunting For Ebola and The Outbreak In The DRC
The hunt for Ebola’s hiding place has eluded scientists since its identification in 1976. Believing that bats are a natural reservoir, many are tracking them throughout the DRC. While we’ve picked apart the virus in BSL-4 labs for decades and continue to learn about its genomics, we’re tragically unable to truly understand the virus in its natural habitat. “But the virus’s natural history is a mystery, says virologist Vincent Munster, sitting outside his tent in the darkening jungle. ‘We know everything about its replication cycle but fricking nothing about where it comes from and how it causes outbreaks’. Earlier in his career, at the Erasmus Medical Center in Rotterdam, the Netherlands, Munster took part in the controversial ‘gain of function’ experiments that engineered the lethal H5N1 bird flu virus to spread more readily among mammals-including, presumably, people. These days, however, Munster talks less about viral genes and proteins than about virus ecology: the web of interactions that allows a zoonotic virus to travel between species. Logging, hunting, and other human encroachment on pristine environments all play a role, bringing people into contact with the microbes that lurk there.” Researchers, like Munster, are sampling animals (especially bats) to try and find a pattern that would explain why they’re most likely to carry the virus and if that might fluctuate. Trying to find the virus in bats is equally challenging despite knowing that they carry it. Interestingly, the virus is wholly dangerous to primates and many consider it the biggest threat to gorillas apart from poaching. During their work, the researchers were alerted to a chimpanzee carcass and throughout their response, they note just how careful they must be when handling it. “It was covered in maggots, Munster says-‘just a huge, pulsating mess.’ Ebola may be scarce in living animals, but carcasses like that one practically explode with virus. ‘We’ve done those studies,’ Munster says. ‘Every cell, every orifice of that carcass is loaded with Ebola.’ To minimize the risk to researchers, Munster helped develop a protocol for collecting samples from dead animals: swabbing the outside instead of using sharp instruments to collect blood or tissue.” While their work continues, so does the latest outbreak of Ebola in the DRC. The most recent WHO situation reports noted a new suspected case and 15 contacts for monitoring. Currently, there are 5 confirmed cases, 3 probable, and 1 suspected. Four patients have died and four have survived, translating to a 50% case-fatality rate. You can also read the latest WHO new report on response efforts in the DRC here.

Pandemics, Bioterrorism, & Global Health Security Workshop Instructor Spotlight
Our instructor spotlight this week will shine on FBI Supervisory Special Agent Edward You. Mr. You is like the action hero of the biological countermeasures world (ok, that might be a tad of an exaggeration, but wait until you read about all the amazing things he does with the FBI!). Mr. You is responsible for creating programs and activities to coordinate and improve FBI and interagency efforts to identify, assess, and respond to biological threats or incidents. These efforts include expanding FBI outreach to the Life Sciences community to address biosecurity. Before being promoted to the Weapons of Mass Destruction Directorate, Mr. You was a member of the FBI Los Angeles Field Office Joint Terrorism Task Force and served on the FBI Hazardous Evidence Response Team. Mr. You has also been directly involved in policy-making efforts with a focus on biosecurity. He is an active Working Group member of the National Security Council Interagency Policy Committee on Countering Biological Threats and an Ex Officio member of the NIH National Science Advisory Board for Biosecurity. He also serves on two committees for the National Academies of Sciences, the Institute of Medicine’s Forum on Microbial Threats and the Committee on Science, Technology, and Law’s Forum on Synthetic Biology. Prior to joining the FBI, Mr. You worked for six years in graduate research focusing on retrovirology and human gene therapy at the University of Southern California, Keck School of Medicine. He subsequently worked for three years at the biotechnology firm AMGEN Inc. in cancer research. Special Agent You works to keep the communication channels open between the synthetic biology community and law enforcement to help identify threats and strengthen relations with the biohacker community. Don’t miss the opportunity to learn from Mr. You and pick his brain during our summer workshop in July!

South Africa’s History of Chemical & Biological Weapons
GMU biodefense alum Glenn Cross is taking a deep dive into the Rhodesian use of chemical and biological weapons from 1975-1980. His recent book, Dirty War, investigates the prevalence of such weapons during the Rhodesian War. During periods of manpower and material shortage, the army would use such unconventional techniques that included planting contaminated food and beverages, medicine, and other goods into guerrilla supplies. “Some of these supplies were provided to guerrilla groups inside Rhodesia; some were transported to guerrilla camps in Mozambique. In all, deaths attributed to CBW agents often exceeded the monthly guerrilla body count claimed by conventional Rhodesian military units – demonstrating the utility of CBW agents in a counterinsurgency campaign against an elusive enemy.” Cross’s investigation is particularly valuable in that knowledge has been spotty and few insiders have been willing to talk. “All (insiders willing to talk) share a consistent story about Rhodesia’s development and use of chemical and biological agents during the Bush War; they even chillingly admit that chemical and biological agents were used in experiments on captured insurgents.”

Tracking Microbes and Inspiring Antibiotic Development
The June 6th WHO statement on the Essential Medicines List (EML) is sending ripples throughout the public health community in regards to antimicrobial resistance. The changes to the EML include the creation of three new categories for antibiotics – ACCESS, WATCH, and RESERVE. These categories include recommendations regarding use and aims to shift prescribing to a more accurate practice. “Initially, the new categories apply only to antibiotics used to treat 21 of the most common general infections. If shown to be useful, it could be broadened in future versions of the EML to apply to drugs to treat other infections. The change aims to ensure that antibiotics are available when needed, and that the right antibiotics are prescribed for the right infections. It should enhance treatment outcomes, reduce the development of drug-resistant bacteria, and preserve the effectiveness of ‘last resort’ antibiotics that are needed when all others fail.” The revision to this list highlights a growing need for antibiotic innovation. BARDA director, Joseph Larsen, hopes to change this and speed up the pace of antibiotic development in the face of growing microbial resistance. Current antibiotic development can take years, cost millions of dollars, and often only generates a profit after 23 years. Larsen notes that there hasn’t been a new class of drugs for treating gram-negative bacilli for over fifty years and that the volume of candidate antibiotics in phase 3/4 trials is barely 10% of those in oncology trials. BARDA is hoping to facilitate innovation through their CARB-X program, “which is one of the world’s largest public-private partnerships focused on developing new antibacterial products. When they started this program, BARDA expected 50 grant applications, but received 368 applications within the first 2 cycles. The goal is to deliver at least 2 antibacterial products to clinical development within 5 years. BARDA is planning on investing $250 million over the next five years to CARB-X.” Antibiotic innovation will become increasingly important as resistance grows, which highlights the importance of tracing microbial movement. GMU biodefense PhD student, Saskia Popescu, is looking at a recent study on hospital bacterial tracing and what that means for infection prevention efforts. Researchers sampled patient rooms prior to a new medical center opening and continued sampling for nearly a year, finding that microbial communities had some interesting trends. While hospital disinfection failures are frequently a source for transmission, it was found that the microbial community shifts after the patient has been in a room for 24 hours. Moreover, researchers found that a majority of admitted patients were on antibiotics and that those with longer stays tended to show an evolutionary shift to resistance. “Overall, this new study highlights the movement of microbes within healthcare and how we can start improving our tactics to help reduce the risk of healthcare-associated infections and blossoming bacterial resistance.” Worst case scenario, we could just always stop shaking hands

Bioterrorism Budget Cuts & DoD Chemical & Biological Defense Annual Report
GMU biodefense PhD alum Daniel M. Gerstein is focusing on just how vulnerable the proposed budget would make the U.S. in the event of a bioterrorism attack. The budgetary cut to NBACC at Ft. Detrick would mean that laboratory and science response to bioterrorism would be significantly gutted without a replacement plan. “The NBACC’s scientists also are capable of conducting experiments to determine what level of concern is warranted if a potential threat is identifiedThe NBACC also has bioforensics analysis capabilities. This provides the ability to understand how and potentially where a pathogen was prepared, its virulence and physical characteristics and even what medical countermeasures and decontamination techniques might be the most effective.” This is especially vital as even the decontamination of a site can be challenging and expensive. The 2001 Amerithrax attacks highlighted these gaps – between responsibility, practices, protocols, and cost, the decontamination of the office buildings and postal handling facilities cost roughly $320 million and pointed out some pretty significant gaps within U.S. bioterrorism response. Gerstein implores policymakers to take a second look at this proposed budgetary cut and decide if leaving the US without these critical capabilities is truly a wise decision. “They should assess whether NBACC’s capabilities, as an insurance policy, is a price worth paying when weighed against the potential cost in human terms of even a limited bioterror attack.”

The 2017 DoD Chemical and Biological Defense 2017 Annual Report to Congress has just been released, which includes specific comments on response to ISIS and synthetic biology activities. Within the report you can find sections on advanced diagnostics, advanced medical countermeasures (check out the section on the cocktail of three monoclonal antibodies developed to fight Ebola), advances in non-traditional chemical agent defense, and more! One of my favorite sections was actually on information systems – “The Global Biosurveillance Portal (G-BSP) program achieved IOC. This capability will provide a web-based, cloud-hosted enterprise environment that will facilitate collaboration, communication, and information sharing in support of the detection, management, and mitigation of man-made and naturally occurring biological events. G-BSP also facilitates the fusion of multiple unclassified information sources for greater situational awareness and decision support.” A recent study published in The Lancet, highlights the importance of diagnostic preparedness. Citing the 2014/2015 Ebola outbreak as a prime example, researchers note that while the diagnostic response eventually worked, it was slow and expensive, which severely impacted outbreak response. “If a focused mechanism had existed with the technical and financial resources to drive its development ahead of the outbreak, point-of-care Ebola tests supporting a less costly and more mobile response could have been available early on in the diagnosis process. A new partnering model could drive rapid development of tests and surveillance strategies for novel pathogens that emerge in future outbreaks. We look at lessons learned from the Ebola outbreak and propose specific solutions to improve the speed of new assay development and ensure their effective deployment.”

Committee on Strategies for Identifying and Addressing Biodefense Vulnerabilities Posed by Synthetic Biology
Don’t miss this July 6th workshop held at the National Academies of Sciences, Engineering, and Medicine’s Keck Center at 500 5th Street NW, Washington DC.  Attendees will hear from several experts and discuss four main topics: human modulation, public health and military preparedness, efficacy of design, and emerging technologies to overcome existing technical barriers. The meeting won’t be webcast or made available virtually, so you’ll want to attend in person.

China’s Battle Against An H7N9 Outbreak
While the outbreak may be slowing, eight new cases were reported this past week. What worries many though are the recent studies published that point to the highly pathogenic variant that was infecting poultry. Currently in its fifth wave of H7N9 activity, Chinese cases are showing a shift to impact more middle-aged adults in rural areas. “In the second report, a team from China described the clinical course and genetic findings in a 56-year-old Guangdong province man who died from a highly pathogenic H7N9 virus that showed a marker for resistance to neuraminidase inhibitors (NIs), the antiviral drugs commonly used to treat influenza.” You can read the press release from the Government of the Hong Kong Special Administrative Region here.

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