Publications

Five years ago, the world was on a precipice. An outbreak of Ebola that had started in Guinea spilled into neighboring Liberia and Sierra Leone. None of the affected countries had recorded an outbreak of Ebola before, and the response was challenged by lack of public health capacities, community distrust of healthcare workers, poor communication, and difficulties reaching affected populations. International health officials expressed concerns about the potential for further spread of the virus throughout the continent, and, ultimately, more than 11,000 people lost their lives.

We propose here changes to the U.S. government policy on potential pandemic pathogen (PPP) oversight and implementation, emphasizing transparency of the review process and the content of the review, publication of the review in advance, responsible publication of enhanced PPP research, high-level signoff on approvals of enhanced PPP experiments, and the need for a signi?cant effort to establish a common international approach to enhanced PPP work. We advocate that the U.S. government recommend, and non-U.S. government funders and journals adopt, a set of best practices that would extend important considerations of biosafety and biosecurity to all work on enhanced potential pandemic pathogens regardless of funding source.

Coronaviruses (CoV) are a family of RNA viruses that typically cause mild respiratory disease in humans. However, the 2003 emergence of the severe acute respiratory disease coronavirus (SARS-CoV) demonstrated that CoVs are also capable of causing outbreaks of severe infections in humans. A second severe CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), emerged in 2012 in Saudi Arabia. More recently, a novel coronavirus was identified in Wuhan, China, in December 2019.

On July 26, 2019, the workshop “Biosafety and Biosecurity in the Era of Synthetic Biology: Meeting the Challenges in China and the U.S.”, co-hosted by Johns Hopkins Center for Health Security and Tianjin University Centre for Biosafety Research & Strategy, was held in Washington, D.C. of the United States. The goal of this workshop was to bring technical and policy experts from China and the U.S., as well as experts from Europe, 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 biosafety and biosecurity.

The scientific enterprise satisfies the innate human urge to understand the world; these efforts have led to both improvements and dangers to society. The storied history of relationships between scientists and citizens suggests that the lines between these 2 sectors of society are often blurred. Here we discuss these relationships on the context of animal welfare. We briefly outline the history of animal welfare in research, and the entry of citizens into the discussion, leading to the Animal Welfare Act of 1966. The commitment of scientists to society, in this context, is the act of whistleblowing in research. As medical and life sciences technologies continue to expand at breathtaking rates, the landscape that both scientists and citizens must navigate increases in complexity. We discuss the responsibility of both the scientist and the citizen, as members of the voting public, in the face of the challenges of the future.

In recent years, interest has grown in gender as a useful analytical perspective to examine the impact of particular means and methods of warfare. Multilateral debates on chemical and biological weapons, however, have not systematically considered the relevance of sex- and age-disaggregated data on the effects of these weapons, nor knowledge of gender dynamics, in the implementation of the Biological and Chemical Weapons Conventions (BWC and CWC, respectively). Such information and perspectives, however, can contribute to States’ preparedness and enhance the effectiveness of assistance under CWC article X and BWC article VII. Moreover, it could help to increase resilience and to aid recovery from chemical or biological incidents. Ultimately, a gender-responsive approach can help States to enhance the security and well-being of all their citizens.

This volume focuses on Global Catastrophic Biological Risks (GCBRs), a special class of infectious disease outbreaks or pandemics in which the combined capacity of the world’s private and government resources becomes severely strained. These events, of which the 1918 influenza pandemic is emblematic, cause severe disruptions in the normal functioning of the world, exact heavy tolls in terms of morbidity and mortality, and lead to major economic losses.

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.