Publications

According to the 2015 Global Burden of Disease Study, diarrhea ranked ninth among causes of death for all ages, and fourth among children under 5 years old, accounting for an estimated 499,000 deaths in this young age group. It was also the second most common cause of years lived with disability (2.39 billion YLDs). The goal of the WHO/UNICEF Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhea (GAPPD) is to reduce deaths from diarrhea in children under 5 years of age to less than 1 per 1000 live births, by 2025. Development of new and improved vaccines against diarrheal infections is a fundamental element of the strategy towards achieving this goal.

We report the heterologous expression, structure, and antimicrobial activity of a lasso peptide, ubonodin, encoded in the genome of Burkholderia ubonensis. The topology of ubonodin is unprecedented amongst lasso peptides, with 18 of its 28 amino acids found in the mechanically bonded loop segment. Ubonodin inhibits RNA polymerase in vitro and has potent antimicrobial activity against several pathogenic members of the Burkholderia genus, most notably B. cepacia and B. multivorans, causative agents of lung infections in cystic fibrosis patients.

Since the inception of gene synthesis technologies, there have been concerns about possible misuse. Using gene synthesis, pathogens—particularly small viruses—may be assembled “from scratch” in the laboratory, evading the regulatory regimes many nations have in place to control unauthorized access to dangerous pathogens. Progress has been made to reduce these risks. In 2010, the US Department of Health and Human Services (HHS) published guidance for commercial gene synthesis providers that included sequence screening of the orders and customer screening. The industry-led International Gene Synthesis Consortium (IGSC) was formed in 2009 to share sequence and customer screening methods, and it now includes the major international gene synthesis providers among its members. Since the 2010 HHS Guidance was released, however, there have been changes in gene synthesis technologies and market conditions that have reduced the efficacy of these biosecurity protections, leading to questions about whether the 2010 HHS Guidance should be updated, what changes could make it more effective, and what other international governance efforts could be undertaken to reduce the risks of misuse of gene synthesis products. This article describes these conditions and recommends actions that governments should take to reduce these risks and engage other nations involved in gene synthesis research.

The 2014–2016 Ebola outbreak was a wake-up call regarding the critical importance of resilient health systems. Fragile health systems can become overwhelmed during public health crises, further exacerbating the human, economic, and political toll. Important work has been done to describe the general attributes of a health system resilient to these crises, and the next step will be to identify the specific capacities that health systems need to develop and maintain to achieve resiliency.

From April 29 to May 1, 2019, the Johns Hopkins Center for Health Security and the Thailand Ministry of Public Health’s Department of Disease Control co-hosted a meeting of the Southeast Asia Strategic Multilateral Biosecurity Dialogue in Phuket, Thailand. This dialogue began in 2014 as a bilateral Track II dialogue between Singapore and the United States and expanded the following year to include Indonesia and Malaysia. The Philippines and Thailand were added as observers in 2017, and they became full participants starting with this year’s meeting. The purpose of this dialogue is to examine biological risks facing the United States and the Southeast Asia region—including natural, accidental, and deliberate. This dialogue aims to facilitate cross-border and regional engagement and collaboration and identify novel solutions and share best practices in combatting priority threats.

We conducted semistructured interviews with individuals directly involved in the response to a mumps outbreak and analyzed outbreak response–associated cost data.

The “community resilience” ideal breaks with earlier status quo thinking that it is enough for society to respond to disasters as they occur. Mounting human and economic losses and a several-decades-long upward trajectory in the extreme events (i.e., tropical storms, flooding, drought, and wildfire) occurring each year have made such a reactionary position no longer tenable. Policymakers, practitioners, and populations now aspire more fully for communities to anticipate, withstand, recover from, and emerge even stronger after a disaster.1

This report examines the current state of preparedness for pandemics caused by “high-impact respiratory pathogens”—that is, pathogens with the potential for widespread transmission and high observed mortality. Were a high-impact respiratory pathogen to emerge, either naturally or as the result of accidental or deliberate release, it would likely have significant public health, economic, social, and political consequences. Novel high-impact respiratory pathogens have a combination of qualities that contribute to their potential to initiate a pandemic. The combined possibilities of short incubation periods and asymptomatic spread can result in very small windows for interrupting transmission, making such an outbreak difficult to contain. The potential for high-impact respiratory pathogens to affect many countries at once will likely require international approaches different from those that have typically occurred in geographically limited events, such as the ongoing Ebola crisis in Democratic Republic of the Congo (DRC).

On July 26, 2019, researchers, policymakers, and other stakeholders gathered at the St. Regis Hotel in Washington, DC, for a day-long dialogue on safety and security in an era of synthetic biology. The meeting, co-sponsored by the Johns Hopkins Center for Health Security and Tianjin University Centre for Biosafety Research and Strategy, drew more than 100 attendees and featured speakers from China, Europe, and the United States.

The United States and China are at the forefront of research and investment in synthetic biology. As leading countries in this rapidly evolving field, they have a responsibility to work together to promote safety and security. The goal of this meeting was to bring representatives from China and the United States together to develop a mutual understanding of each country’s current governance structures and to begin a dialogue on what is required to promote global safety and security. This report recounts the meeting’s activities and shares several key themes derived from the presentations and conversations of the day.

We conducted semistructured interviews with health officials from 9 city or county health departments to collect the firsthand experience of public health responders. We collected data from January to October 2018 via teleconference. Key informants, whom we purposefully sampled, were senior public health officials who were directly involved in outbreak response or in preparing for potential hepatitis A outbreaks in their communities.

The use of PrEP has revolutionized the response to HIV. If this success can be replicated for other STIs — which are on a major upswing — it would be a major win in the battle against these infections. Although the evidence base is not strong, there is an important positive signal that needs to be studied more systematically to demonstrate benefit and assess the risk of antimicrobial resistance with widespread use of antibiotic-based therapies. However, it may be a feasible strategy in high-risk populations if coupled to surveillance for resistance among targeted infections. STIs such as gonorrhea, chlamydia, and syphilis have slipped out of control and having an effective pharmaceutical preventive measure could significantly diminish the force of infection and reverse the worrying trend currently occurring.

Present capacity to develop, evaluate, manufacture, distribute and administer effective medical countermeasures (e.g., vaccines, diagnostics, therapeutics) is inadequate to meet the burden of both recurrent and emerging outbreaks of infectious diseases. When such interventions are unavailable, public health measures (e.g., contact tracing, outbreak investigations, social distancing) and supportive clinical care remain the only feasible tools to slow an emerging outbreak. Decision-making under such circumstances can be greatly improved by the use of appropriate data and advanced analytics such as infectious disease modeling or machine learning. Furthermore, these analyses can guide decision-making when medical countermeasures become available, allowing them to be used in more effective ways. Data analyses already underpin public health actions such as anticipating resource requirements, refining situational awareness and monitoring control efforts^2,3,4,5. New applications of data science and statistical analyses to disease outbreaks could provide support to decision-makers during public health crises.

Advances in biotechnology in the twenty-first century, fueled in large part by the field of synthetic biology, have greatly accelerated capabilities to manipulate and re-program bacteria, viruses, and other organisms. These genetic engineering capabilities are driving innovation and progress in drug manufacturing, bioremediation, and tissue engineering, as well as biosecurity preparedness. However, biotechnology is largely dual use, holding the potential of misuse for deliberate harm along with positive applications; defenses against those threats need to be anticipated and prepared. This chapter describes the challenges of managing dual-use capabilities enabled by modern biotechnology and synthetic biology and highlights a framework tool developed by a National Academies committee to aid analysis of the security effects of new scientific discoveries and prioritization of concerns. The positive aspects of synthetic biology in preparedness are also detailed, and policy directions are highlighted for taking advantage of the positive aspects of these emerging technologies while minimizing risks.

Predicting which pathogen will confer the highest global catastrophic biological risk (GCBR) of a pandemic is a difficult task. Many approaches are retrospective and premised on prior pandemics; however, such an approach may fail to appreciate novel threats that do not have exact historical precedent. In this paper, based on a study and project we undertook, a new paradigm for pandemic preparedness is presented. This paradigm seeks to root pandemic risk in actual attributes possessed by specific classes of microbial organisms and leads to specific recommendations to augment preparedness activities.

This year marks the 165th anniversary of the Broad Street cholera outbreak, which resulted in more than 500 deaths in the Soho neighborhood of London. This outbreak marked a critical turning point in both public and academic perception of disease transmission when it became known that cholera was being transmitted through a specific water pump. John Snow, a medical doctor, created a simple spot map to identify the Broad Street pump as the most likely source of the outbreak. Thus, spatial/temporal modeling became foundational in epidemiology and continues to be vital to modern outbreak investigations. Since 1854, mapping techniques and data imaging have greatly evolved in complexity, accessibility, and flexibility, such that they may be applied to a wide range of public health issues.

Research with animals presents a wide array of hazards, some of which overlap those in the in vitro research laboratory. The challenge for environmental health and safety professionals when making their recommendations and performing the risk assessment is to balance worker safety with animal safety/welfare. The care and husbandry of animals require procedures and tasks that create aerosols and involve metabolized chemicals and a variety of physical hazards that must be assessed in addition to the research related risks, all while balancing the biosecurity of the facility and NIH animal care requirements. Detailed communication between health and safety, research, and animal care teams is essential to understand how to mitigate the risks that are present and if modifications need to be made as the experiments and processes progress and change over time. Additionally, the backgrounds and education levels of the persons involved in animal research and husbandry can be quite broad; the training programs created need to reflect this. Active learning and hands-on training are extremely beneficial for all staff involved in this field. Certain areas of research, such as infectious disease research in high- and maximum-containment (biosafety level 3 and 4) facilities, present challenges that are not seen in lower containment or chemical exposure experiments. This paper reviews potential hazards and mitigation strategies and discusses unique challenges for safety at all biosafety levels.

Testing of 14 patients with acute flaccid myelitis, or AFM, showed they had antibodies against enteroviruses, especially EV-D68, in their cerebrospinal fluid at a significantly higher rate than controls, supporting “the plausibility of a link” between enterovirus infection and AFM, researchers reported in mBio.

On July 16, the Johns Hopkins Center for Health Security and Ginkgo Bioworks convened a meeting in Washington, DC, to solicit stakeholder input on specific ways that national policy can strengthen the US bioeconomy. For the purposes of this meeting, the bioeconomy was defined broadly as the economy built on biotechnology. There currently is no consensus on a definition of bioeconomy, but most accept that it encompasses parts of the energy, agriculture, medical, industrial, and defense sectors. The aims of the meeting were to consider the benefits to the US if its bioeconomy were to be expanded; examine the current health of the US bioeconomy; discuss existing US government programs, policies, and initiatives related to the bioeconomy; and identify priorities for strengthening the US bioeconomy.

This paper considers approaches to risk and benefit assessment that could be applied to advances in the life sciences with possible “dual-use” implications for bioweapons development. The paper describes the components of scientific risk assessment and outlines existing risk assessment tools of particular relevance to the Biological Weapons Convention, including those developed by the U.S. National Science Advisory Board for Biosecurity (NSABB), Jonathan B. Tucker, and the U.S. National Academy of Sciences. Finally, it highlights additional risk management tools and discusses approaches to weighing benefits.

Since the 2014–2016 West Africa Ebola epidemic, the concept of measuring health security capacity has become increasingly important within the broader context of health systems-strengthening, enhancing responses to public health emergencies, and reducing global catastrophic biological risks. Efforts to regularly and sustainably track the evolution of health security capabilities and capacities over time – while also accounting for political, social, and environmental risks – could help countries progress toward eliminating sources of health insecurity. We sought to aggregate evidence-based principles that capture a country’s baseline public health and healthcare capabilities, its health security system performance before and during infectious disease crises, and its broader social, political, security, and ecological risk environments.