Publications

The global burden of infectious diseases and the increased attention to natural, accidental, and deliberate biological threats has resulted in significant investment in infectious disease research. Translating the results of these studies to inform prevention, detection, and response efforts often can be challenging, especially if prior relationships and communications have not been established with decision-makers. Whatever scientific information is shared with decision-makers before, during, and after public health emergencies is highly dependent on the individuals or organizations who are communicating with policy-makers. This article briefly describes the landscape of stakeholders involved in information-sharing before and during emergencies. We identify critical gaps in translation of scientific expertise and results, and biosafety and biosecurity measures to public health policy and practice with a focus on One Health and zoonotic diseases. Finally, we conclude by exploring ways of improving communication and funding, both of which help to address the identified gaps. By leveraging existing scientific information (from both the natural and social sciences) in the public health decision-making process, large-scale outbreaks may be averted even in low-income countries.

The presence of bottlenecks in the transmission cycle of many RNA viruses leads to a severe reduction of number of virus particles and this occurs multiple times throughout the viral transmission cycle. Viral replication is then necessary for regeneration of a diverse mutant swarm. It is now understood that any perturbation of the mutation frequency either by increasing or decreasing the accumulation of mutations in an RNA virus results in attenuation of the virus. To determine if altering the rate at which a virus accumulates mutations decreases the probability of a successful virus infection due to issues traversing host bottlenecks, a series of mutations in the RNA-dependent RNA polymerase of Venezuelan equine encephalitis virus (VEEV), strain 68U201, were tested for mutation rate changes. All RdRp mutants were attenuated in both the mosquito and vertebrate hosts, while showing no attenuation during in vitro infections. The rescued viruses containing these mutations showed some evidence of change in fidelity, but the phenotype was not sustained following passaging. However, these mutants did exhibit changes in the frequency of specific types of mutations. Using a model of mutation production, these changes were shown to decrease the number of stop codons generated during virus replication. This suggests that the observed mutant attenuation in vivo may be due to an increase in the number of unfit genomes, which may be normally selected against by the accumulation of stop codons. Lastly, the ability of these attenuated viruses to transition through a bottleneck in vivo was measured using marked virus clones. The attenuated viruses showed an overall reduction in the number of marked clones for both the mosquito and vertebrate hosts, as well as a reduced ability to overcome the known bottlenecks in the mosquito. This study demonstrates that any perturbation of the optimal mutation frequency whether through changes in fidelity or by alterations in the mutation frequency of specific nucleotides, has significant deleterious effects on the virus, especially in the presence of host bottlenecks.

This chapter provides an overview of the scientific, policy, and operational issues involved in environmental remediation of a biological weapons attack, with a significant focus on US programs and policies. The chapter introduces the topic of biological remediation by defining the process and exploring biological agents of concern and their persistence in the environment. Past biological remediation examples are briefly discussed, followed by a review of past and current remediation policies and practices, as well as knowledge gaps and future research direction.

Synthetic biology and other advanced biotechnologies hold a great deal of promise for medicine, public health, manufacturing, and national economies, but they also have biosafety and biosecurity implications. Using synthetic biology techniques, it is possible for a nefarious actor to acquire a viral pathogen made with chemically synthesized pieces, versus having to acquire samples of pathogens from an environmental source or from another laboratory. It is also possible to test many parallel approaches for designing new functions into existing pathogens, given that the costs of DNA synthesis continue to drop; this has dual-use implications for biodefense. These biosecurity concerns do not replace the existent challenges prior to the advent of synthetic biology but add to them, as early non-synthetic biology paths to biological weapons development are still able to be used to make biological weapons. In addition to biosecurity concerns, there are biosafety implications of synthetic biology, as the techniques are powerful, they may be used outside of traditional biocontainment, and because relative newcomers to biological containment are entering the field.

On December 3, 2018, the Johns Hopkins Center for Health Security convened the first annual Global Forum on Scientific Advances Important to the Biological and Toxin Weapons Convention, coinciding with the 2018 Meeting of States Parties to the Biological and Toxin Weapons Convention (BWC MSP) in Geneva, Switzerland. The forum had 2 purposes: (1) to inform States Parties’ delegations of cutting-edge biological capabilities, including the ability to engineer pathogens or more complex organisms, and (2) to build awareness of and support for international bioweapons nonproliferation norms among the scientific community. Advanced biology, engineered pathogens and other organisms, and accidental biological threats as sources of risk are of great concern to international biological nonproliferation regimes such as the BWC.

In 2017-18, the Johns Hopkins Center for Health Security conducted a multiphase research project to help inform the development of a strategic approach for communicating about global catastrophic biological risks (GCBRs). In brief, we define a GCBR as a biological development that could adversely affect the human species as a whole or radically change the course of human civilization—for instance, a severe pandemic involving a naturally occurring or deliberately engineered pathogen. GCBRs are an emerging concern among a discrete set of scientists and organizations located principally in Europe and the United States. To conceive and implement activities necessary to prevent or respond to biological threats of a global scale will require effective communication of the issue’s importance—internationally—to a range of people with knowledge, influence, and control of resources.

December 2018 marked the fifth anniversary of the start of the worst Ebola epidemic in recorded history. The epidemic spread rapidly from rural villages in Guinea to major cities across West Africa,¹ ultimately resulting in 28,652 cases and 11,325 deaths across 10 countries,² including the first known transmission of Ebola virus infection outside of Africa.³ Despite the declaration of a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) in August 2014,⁴ the international response lagged. The epidemic peaked in October 2014,⁵ but another 20 months passed before WHO issued its final declaration of the end of the epidemic in June 2016.⁶ Even before the official end of the epidemic, WHO announced major organizational and operational reforms in response to the challenges faced during the global epidemic response,^7,8 and public health and healthcare organizations around the world, including those that treated Ebola virus disease (EVD) patients, initiated efforts to increase preparedness for Ebola and other high-consequence infectious diseases (HCIDs).

The epidemic of Ebola virus disease in the Democratic Republic of the Congo (DRC) is the second largest in history after the 2014 west African epidemic. A storm of detrimental factors complicates this event: armed conflict, political instability, and mass displacement. WHO, the DRC Government, and non-governmental organisation (NGO) partners have shown remarkable leadership but are badly stretched. The outbreak remains far from controlled, risking a long-term epidemic with regional, perhaps global, impacts.

The 2014–16 West Africa Ebola epidemic was a watershed moment for global health. The outbreak galvanized global action around strengthening infectious disease prevention, detection and response capabilities. We examined the nascent landscape of international programmes, initiatives and institutions established in the aftermath of the 2014–16 Ebola outbreak with the aim of assessing their progress to date to illustrate the current state of the world’s global health security architecture. We also compare these efforts with shortcomings in epidemic management documented during the epidemic, and underscore remaining gaps in regional and global epidemic response capabilities that might benefit from additional programmatic and financial support. Notably, most of the post-Ebola initiatives considered in this analysis have yet to meet their financial goals. Operational progress has also been limited, revealing a need for continued investments to improve outbreak surveillance and detection capabilities specifically. Furthermore, our review highlighted the dominance of the USA and Europe in leading and financing efforts to coordinate long-term recovery efforts in West Africa, strengthen health systems across the continent, and enhance global preparedness for future epidemics, raising important questions about ownership of global health security efforts in non-Western regions of the world. Finally, the lack of transparency and available data on these initiatives’ activities and budgets also complicate efforts to project their impacts on the global health security landscape.

In September 2018, the Johns Hopkins Center for Health Security (“the Center”) hosted a dialogue on biosecurity between experts from the United States and the Republic of India. The dialogue, which was held in Washington, DC, was organized in collaboration with the DBT-UNESCO Regional Centre for Biotechnology, an autonomous institute of the Department of Biotechnology (part of the Ministry of Science and Technology, Government of India). This was the fifth meeting of the dialogue, following previous engagements in Washington, DC, in September 2016 and November 2017, as well as meetings in New Delhi, India, in February 2018 and February 2017.This effort is supported by the Project on Advanced Systems and Concepts for Countering WMD (PASCC, which is sponsored by the Defense Threat Reduction Agency, DTRA) of the US Air Force Institute for National Security Studies.

This report highlights 15 technologies or categories of technologies that, with further scientific attention and investment, as well as attention to accompanying legal, regulatory, ethical, policy, and operational issues, could help make the world better prepared and equipped to prevent future infectious disease outbreaks from becoming catastrophic events.

The Johns Hopkins Center for Health Security conducted a Track II multilateral biosecurity dialogue between Singapore, Malaysia, Indonesia, and the United States—with observers from the Philippines and Thailand—in Nusa Dua, Indonesia on April 18-20, 2018. Dialogue topics included national biosecurity priorities as well as ongoing and emerging biosecurity threats facing Southeast Asia countries, ranging from emerging infectious diseases to advances in biotechnology to bioterrorism. Participants discussed national-level biosecurity programs and shared lessons from their experiences, building on trusted relationships established over several years of this dialogue with the aim of improving national capacity and collaboration across the broad scope of biosecurity issues.

The Johns Hopkins Center for Health Security conducted this study to elucidate the characteristics of naturally occurring microorganisms that constitute a global catastrophic biologic risk (GCBR).

GCBRs are defined as “those events in which biological agents—whether naturally emerging or reemerging, deliberately created and released, or laboratory engineered and escaped—could lead to sudden, extraordinary, widespread disaster beyond the collective capability of national and international governments and the private sector to control. If unchecked, GCBRs would lead to great suffering, loss of life, and sustained damage to national governments, international relationships, economies, societal stability, or global security.”

Every few years, a new pathogen emerges from the shadows to threaten global public health. And every few years, the global public health community struggles to mount a timely and effective response. The incremental advances that have defined public health in the last half century have been repeatedly outpaced by fast-moving epidemics. From HIV to Ebola, most innovations in preventing and containing outbreaks have come from medical countermeasures like vaccines, diagnostics, and therapeutics rather than advancements in epidemiological practice.

In February 2018, the Johns Hopkins Center for Health Security (“the Center”) hosted a Track II dialogue on biosecurity between experts from the United States and the Republic of India. The dialogue, which was held in New Delhi, India, was organized in collaboration with the DBT-UNESCO Regional Centre for Biotechnology, an autonomous institute of the Department of Biotechnology (part of the Ministry of Science and Technology, Government of India). This was the fourth meeting of the dialogue, following previous engagements in Washington, DC, in September 2016 and November 2017, as well as a meeting in New Delhi, India, in February 2017.1,2,3 This effort is supported by the Project on Advanced Systems and Concepts for Countering WMD (PASCC, which is sponsored by the Defense Threat Reduction Agency, DTRA) of the US Air Force Institute for National Security Studies.

In November 2017, the Johns Hopkins Center for Health Security (“the Center”) hosted a Track II dialogue (i.e. a non-governmental engagement) on biosecurity between experts from the United States and the Republic of India. The dialogue, which was held in Washington, DC, was organized in collaboration with the Department of Biotechnology (part of the Ministry of Science and Technology, Government of India). This was the third meeting of the dialogue; the first was held in Washington, DC in September 2016, and the second in New Delhi, India, in February 2017. The effort is supported by the Project on Advanced Systems and Concepts for Countering WMD (PASCC, which is sponsored by the Defense Threat Reduction Agency, DTRA) of the US Air Force Institute for National Security Studies.

The following narrative comprises a futuristic scenario that illustrates communication dilemmas concerning medical countermeasures (MCMs) that could plausibly emerge in the not-so-distant future. Its purpose is to prompt users, both individually and in discussion with others, to imagine the dynamic and oftentimes conflicted circumstances in which communication around emergency MCM development, distribution, and uptake takes place. While engaged with a rigorous simulated health emergency, scenario readers have the opportunity to mentally “rehearse” responses while also weighing the implications of their actions. At the same time, readers have a chance to consider what potential measures implemented in today’s environment might avert comparable communication dilemmas or classes of dilemmas in the future.

In February 2017, the Johns Hopkins Center for Health Security hosted a Track II (non- governmental) dialogue on biosecurity between experts in India and the US in New Delhi, India. The meeting was held in collaboration with the Department of Biotechnology within the Indian Ministry of Science and Technology. This was the second meeting of the biosecurity dialogue; the first was held in Washington, DC in September, 2016.* The effort is supported by the Project on Advanced Systems and Concepts for Countering WMD (PASCC; sponsored by the Defense Threat Reduction Agency, DTRA) of the US Air Force Institute for National Security Studies.

Although the healthcare system is undoubtedly better prepared for disasters than it was before the events of 9/11, it is not well prepared for a large-scale or catastrophic disaster. Just as important, other segments of society that support or interact with the healthcare system and that are needed for creating disaster-resilient communities are not sufficiently prepared for disasters. This report is the culmination of a 2-year project funded by the Robert Wood Johnson Foundation to examine US disaster healthcare with the purpose of identifying changes, innovations, and new efforts that could strengthen the country’s ability to provide medical care in major disasters. In the report, Johns Hopkins Center for Health Security researchers analyze a range of disasters that could confront the United States and consider their impacts on the healthcare system, including how medical care would be delivered in those scenarios, both to victims of the disaster and everyone else. We found that many of the current programs are quite valuable and should continue to be supported, and that several new initiatives should be pursued that would improve the disaster readiness and resilience of the US health sector.

On December 2-3, 2015, the UPMC Center for Health Security hosted the second meeting of Track II biosecurity dialogue between the United States, Singapore, Malaysia, and Indonesia. The meeting took place in Kuala Lumpur, Malaysia and was co-sponsored by the Malaysian Ministry of Health (MOH). The dialogue is supported by the Project on Advanced Systems and Concepts for Countering WMD (PASCC) of the Center on Contemporary Conflict, sponsored by the US Defense Threat Reduction Agency (DTRA).

The purpose of the second meeting of the dialogue – which is the focus of this report – was to engage participants in deeper conversations around the unique biosecurity landscapes of Singapore, Malaysia, Indonesia, and the US; examine ongoing national, regional, and global biosecurity threats; identify and critique current policies and approaches to biological threat mitigation; and exchange best practices in biorisk management to strengthen responses to emerging and evolving biological threats. The dialogue featured participants representing various levels of academia, and government, including experts in the life sciences, defense, public health, animal health, journalism, medicine, terrorism, and security.