Clade X: A Pandemic Exercise

Impetus for and Goals of the Project

The exercise was motivated by widespread concern about the potentially devasting consequences of pandemics, as well as the advent of tools in synthetic biology that could be used to engineer dangerous pathogens and could either accidentally or intentionally spark a pandemic. The objective of Clade X was to shine light on policy solutions that could substantially improve preparedness.

Effective policies are born of deeply informed answers to the right questions. The 2 previous pandemic exercises led by the Center—Atlantic Storm ² and Dark Winter ³ —showed that strategic tabletop exercises designed to engage the attention of national leaders can have a lasting impact when they resonate with the intended audience, are well researched and scientifically plausible, and are accessible to the press.

The goals of Clade X were to show the potential consequences of a pandemic, highlight the challenges it would pose, and produce policy solutions that could help prevent or change the outcomes. We intended to show how leaders in public health, politics, law, diplomacy, defense, homeland security, and intelligence all need to work together to solve some of the problems a pandemic will cause. Clade X was not intended to test the technical capabilities of either the players or their respective organizations; rather, it was intended to expose gaps in national and international policy that leave the world vulnerable to the consequences of a severe pandemic.

Through the exercise, we highlighted important issues that remain unresolved from recent actual infectious disease outbreaks, but which could be solved for future outbreaks with sufficient political will and attention. These issues were carefully incorporated into a compelling narrative that would engage the 9 participants, the invited in-person audience of 150 people, and the much larger viewership watching the livestream of the exercise from more than 40 countries.

Summary of the Exercise Scenario

The Clade X storyline begins with concurrent outbreaks of a novel parainfluenza virus in Frankfurt, Germany, and Caracas, Venezuela. Initial evidence indicates that the virus is moderately contagious, principally through respiratory droplets. As it is unclear how this virus is related to other parainfluenza strains, scientists refer to it as “parainfluenza clade X.” It is soon revealed that the virus is in fact a Nipah/parainfluenza hybrid, but it is initially unclear whether this is a natural occurrence or an intentional, genetically engineered mutation.

The virus spreads globally, with the number of cases doubling approximately every 2 weeks and quickly overwhelming public health and medical capacity. Crises pile up rapidly: US soldiers stationed overseas are becoming ill, and the first US cases occur on a small college campus after the return of a foreign exchange student from Germany. Routine antivirals appear to be largely ineffective against the virus, and researchers estimate it will take more than a year before a vaccine will become available. Half of those infected present with severe neurological symptoms, including encephalitis, and about 20% of those exhibiting severe symptoms succumb to the disease.

Later in the course of the exercise, an extremist group claims responsibility for the genetic engineering and deliberate release of the virus. Ultimately, a vaccine is developed and distributed throughout the globe, but not in time to prevent a catastrophic pandemic that sickens hundreds of millions and kills 1 in 10 who become infected.

Exercise Play

Throughout the exercise, information was provided to the EXCOMM players via simulated news clips, simulated briefings from the Centers for Disease Control and Prevention (CDC) and other US departments and agencies, and updates (injects) from each player's respective “staff.” The day-long exercise was split into 4 EXCOMM sessions, each session representing a different time point in the pandemic over the course of 3 months. During these sessions, players discussed controversial policy, political, and ethical challenges faced in responding to the growing pandemic and provided recommendations to the president, who was off stage. Discussion topics included:

A global system that is largely unable to rapidly detect, prevent, and respond to infectious disease emergencies;

Exercise Development

The project development process started in May 2017, 1 year before the event. We began by identifying the overall goals and the intended audience. This was necessary because the learning objectives could vary considerably depending on the target audience. We identified 4 intended audiences: the participants (the individuals playing roles in the exercise), the observers (invited subject matter experts and government officials), the broader health security policy community, and the general public (including the media). With the above-stated goals and these audiences in mind, we crafted and refined learning objectives through an iterative process of team meetings and scenario development and review.

An exercise like Clade X must be credible to be effective. To that end, we conducted extensive research to develop the back story of the Clade X virus, model the epidemiology of the event, and elucidate the societal consequences that would accompany a catastrophic pandemic. The exercise development team included infectious disease physicians and experts in synthetic biology, biosecurity, and public health. A computational epidemiologist on the team developed an epidemiologic model of the Clade X pandemic based largely on parameters from the 2003 SARS pandemic. The output of this model guided the narrative, and, as was the case with the rest of the scenario, the model was updated iteratively to account for evolving objectives and scenario timelines. We also carefully researched and documented domestic and international public health and healthcare response capabilities, drawing on lessons from the 2014-2016 West Africa Ebola outbreak, the 2009 H1N1 influenza pandemic, and the SARS outbreak.

Having the right players is essential to a successful exercise like Clade X. The participants must be knowledgeable and experienced in roles similar to the parts they are playing. We began the recruitment process 6 months in advance of the exercise, identifying potential participant roles—driven by scenario objectives—and lists of potential participants for each. Explicit attention was paid to ensuring a relative balance of political parties (with respect to the administrations under which the prospective participants served) to promote exercise discussions that would accurately reflect real-world conflicts and challenges. We provided the participants with limited briefing materials in advance of the exercise so that they had just enough background information to get the exercise started smoothly but not so much that the element of surprise and tension were lost.

Educational Themes Built into the Scenario

In the year-long process of developing the exercise, we identified a number of learning objectives that were derived from actual disease outbreaks in recent years. The following themes were built into the Clade X scenario:

Key Themes that Emerged

In addition to the learning objectives that were woven into the exercise, a number of themes emerged from discussions among participants during the exercise. These included (organized by category):

US Healthcare System

Policy Recommendations

Following the Clade X exercise, the Center incorporated the key themes above into a series of high-level policy goals for the country that could, over time, help to prevent this kind of pandemic or mitigate its effects.

To prevent a serious epidemic of a novel pathogen from becoming a pandemic, we need the ability to produce a large quantity of safe and effective medical countermeasures within a few months of outbreak recognition. The US government has dedicated substantial resources to developing and stockpiling medical countermeasures for a range of known biological threats. However, we do not have the capacity to rapidly develop large quantities of vaccines, therapeutics, or diagnostics for new and unknown diseases. In fact, for novel diseases or diseases with no previously developed vaccines, the average timeline for vaccine development has historically been a decade or longer. Even for influenza—a virus we are familiar with and make vaccines against regularly—with existing manufacturing technologies, we are not likely to have enough vaccine to substantially change the trajectory of a pandemic before it naturally begins to wane.

Fortunately, advances in biological science and biotechnology could soon enable rapid MCM development, manufacturing, and administration. Recent developments in synthetic biology and investments in synthetic biology foundries are yielding new possibilities for rapid discovery of effective drugs and vaccines. Similarly, novel vaccine technologies, like self-amplifying mRNA vaccines and recombinant vaccines, have shown promise as platforms to enable rapid MCM development during an emergency.

Manufacturing technologies are also improving with scientific advancement in this space. For example, organism like yeast can be engineered to rapidly produce chemical and biologic components of therapeutics and vaccines, and 3D printing can be used to produce chemical compounds on demand. Manufacturing can now be more flexible and distributed, allowing more people in more places to produce and scale MCM production. And novel technologies, such as microarray patches and new oral vaccines, could make mass dispensing and administration of MCMs easier, including by eliminating the need for qualified clinicians to administer vaccinations or by eliminating the need to maintain cold chain during distribution.

These nascent technologies and methods already exist and have the potential to dramatically improve or accelerate our ability to develop, manufacture, distribute, and administer MCMs in response to outbreaks of novel pathogens. But the US government needs a greater level of investment in its MCM enterprise to realize the goal of developing and producing safe, effective MCMs within months rather than years. We echo calls from the 2016 President's Council of Advisors on Science and Technology ⁴ and by National Institute of Allergy and Infectious Diseases Director Dr. Tony Fauci and colleagues ⁵ for increased attention to and uptake of new MCM technologies and methods.

To stop epidemics from becoming pandemics, countries everywhere must have the ability to rapidly detect and effectively respond to infectious disease outbreaks. These capabilities are at the heart of the IHRs. While most countries have signed onto the IHRs, few have achieved full compliance. The United States, in collaboration with the WHO and other nations, should strengthen efforts to promote full achievement of the IHR goals. This can be done in part through programs like the Global Health Security Agenda; participation in the WHO's Joint External Evaluation process; and efforts to develop, fund, and implement global health security priorities in a follow-on US National Action Plan. The greatest health threats often come from the least prepared and most poorly resourced countries. Therefore, it is in the self-interest of all countries to invest in establishing and maintaining the public health capabilities of other less well-prepared countries.

Beyond improving response capabilities in each country, international response coordination for health emergencies must be improved. This includes the coordinated response to outbreaks by national governments and international teams of clinicians and public health professionals. The United States and other countries have provided and should continue to provide substantial international assistance when necessary. This aid can take the form of public health support (eg, epidemiology, risk assessment, emergency operations center response) and provision of materiel, as happened during the West Africa Ebola response. What is much less developed is the capability for the United States to provide clinical care during infectious disease epidemics. Today, the world relies on a limited number of nongovernmental organizations (NGOs) (eg, Médecins Sans Frontières and the International Medical Corps), WHO, and some national medical teams from countries other than the United States to supplement direct patient care during infectious disease outbreaks. The US government should develop a deployable clinical capability to support the response to international infectious disease emergencies. Establishing this capability in the United States should be viewed as vital to the national interest in order to control infectious disease epidemics before they cross international boundaries. Such teams could function either independently or in support of the WHO's emergency medical team initiative.

Local, state, and federal public health comprise the majority of our national response capacity for pandemics. Public health agencies at the local, state, territorial, tribal, and federal levels have been diminished by years of budgets that are far too small for their growing missions. To respond effectively to a pandemic, we need a well-trained, capable, and agile public health workforce. There must be annual preparedness funding to power the public health preparedness infrastructure as well as a substantial emergency response fund to allow immediate response to crises. This investment will foster the kinds of fundamental public health capabilities needed to control an infectious disease outbreak, like strong surveillance and disease detection, rapid infectious disease modeling capacity, medical countermeasure dispensing capacity, effective risk communication, and robust laboratory capacity.

A specific priority for pandemic preparedness is the need for the federal government—together with state and local governments, public stakeholder groups, and scientific experts—to develop clear, effective plans regarding whether and how quarantine would be used. Political leaders have called for quarantines in the past for a myriad of infectious disease threats, but their value and possible consequences have not been sufficiently studied or understood. A national plan for quarantine in the setting of a pandemic should incorporate the best scientific evidence, lessons from past uses of quarantine, and substantial public input. More work needs to be done to provide legal clarity to questions of preemption and transfer of authority during quarantine and to ensure necessary checks and balances exist.

A national plan for quarantine should anticipate potential adverse consequences, including potential public resistance and extraordinary logistical challenges. Plans for managing potential points of contention between policymakers and various levels of government should be established in advance. Appropriate expert legal advice should be available for both policymakers and those potentially affected by such measures. And fast due process for affected members of the public should be assured, or policymakers run the risk of harming public trust, a vital component in a successful response to a pandemic.

With a better resourced public health system across the country, broadly capable of effectively managing infectious disease crises, these events are more likely to be controlled quickly so they do not grow into a severe epidemic or pandemic.

During a catastrophic pandemic, no single entity will be solely responsible for or capable of mounting the response. Collaboration will be required, both prior to and during the event, between relevant health sector entities—including public health, healthcare facilities, emergency medical services, nongovernment and community organizations, elected officials, law enforcement, and the public. In the complex conditions of a pandemic, strict government command and control is unlikely to be effective. Therefore, to ensure our national capacity to effectively respond to a pandemic, relevant entities—both within and outside the health sector—need to fully understand their roles and expected actions well before the onset of such an event. This is especially true of the vast majority of the healthcare system that resides in the private sector.

A proactive and dedicated effort is required to identify individual, facility, and agency roles and responsibilities; form necessary interagency and cross-sectoral relationships; facilitate multi-sectoral collaboration; and establish metrics for assessing the nation's resilience to this type of disaster. Leadership from the highest levels of the federal government and input from the many sectors involved with healthcare response will be needed to fully map the complex requirements that will arise in a pandemic, including the plan for maintaining operational and financial systems in healthcare facilities despite enormous pressures and fear.

The engineered virus that was used as a weapon in this exercise is fictional and would require considerable expertise and resources to produce at this time. But powerful biological techniques, including highly specific methods for gene editing, have been rapidly democratized and are accessible. There are safety risks and risks of misuse that are not the province just of nation states, but of nonstate actors, as in this scenario, or even individuals. Few countries in the world have developed a workable strategy to manage the potential safety and risks of misuse of these new biological methods while also promoting their use for beneficent purposes. An accident or deliberate weaponization involving pathogens that have the potential to spread could have dire global consequences, as represented in the Clade X exercise. Ideally, there should be an international harmonization in national strategic approaches to addressing these risks: The biological sciences are pursued in every part of the world, and it is acknowledged by many security experts that the potential for deliberate or accidental misuse is therefore everywhere. The risks of accident or deliberate misuse would be global. Progress to diminish these risks will be made through internationally coordinated efforts. A chain is only as strong as its weakest link.

These efforts should include a process for surveying scientific advances and objectively evaluating biosecurity risks; the recent National Academies report Biodefense in an Age of Synthetic Biology offers one such framework to evaluate new biotechnologies for their potential to reduce barriers to weaponization. Awareness should be raised in the global science community that scientific work could be misused and that scientists are in the best position to detect whether the work is being pursued in an unsafe manner. Scientists should be given the tools to create new norms of scientific practice, discourage irresponsible risks, and have paths for alerting and for responsible action should they become concerned about what they are seeing or hearing in their institutions or in their broader networks. Scientific journals should be engaged in the discussions, as well; they have had to deal with biosecurity issues intermittently over the years and have had little or no guidance from governments on how to manage them.

The introduction of an infectious disease that transmits readily and has moderate-to-high lethality would simultaneously be a threat to public health and to US national security. As events like the 2001 anthrax attacks and the 2014-2016 West Africa Ebola epidemic demonstrate, biological threats are a source of strategic risk and surprise for the US national security community. ⁶ At the White House level, national and global health security should continue to be a high priority for both the National Security Council and the Office of Science and Technology Policy. In addition, the Departments of Defense, State, Health and Human Services, Homeland Security, and Justice, as well as the agencies that comprise the US intelligence community, have distinct and critical biosecurity assets and responsibilities that should continue to be recognized in national-level plans and strategies and be resourced appropriately by Congress. These departments and agencies should also forge stronger partnerships between the health and security sectors, including the military. In addition, there is a need for professionals with health, medical, and life science expertise to enter government service and bolster government capabilities and expertise at the health-security nexus. Finally, a severe pandemic like the one depicted in this exercise would significantly degrade the ability of national security agencies to function as intended, and additional planning should be dedicated to mitigating and minimizing the worst first, second, and third order effects of a potentially catastrophic pandemic.

OPEN IN VIEWER

Figure 1.

Briefing to the EXCOMM on the Initial Outbreaks of Clade X

Conclusions

The Clade X exercise achieved its first goal of raising awareness and demonstrating the potential cascading consequences of a severe pandemic. The exercise was covered by major national and international news outlets, including the Washington Post, ⁷ The New Yorker, ⁸ Al Jazeera, ⁹ and the Toronto Sun. ¹⁰ The video on YouTube has had more than 16,000 views, and more than 300,000 people have viewed the Al Jazeera (AJ+) story about the exercise on Facebook. In addition, Clade X has led to a series of follow-on presentations and events with the US Congress, the Biological Weapons Convention Meeting of Experts, the CDC, the Aspen Institute, and other organizations.

The second goal of the Clade X project was to make real progress toward reducing the risks associated with a severe pandemic. The high-level policy goals described above are only a starting point, as each of these will require a great deal of additional work to achieve. We at the Johns Hopkins Center for Health Security will devote time and effort in the coming months and years to developing initiatives that progress these goals. Where solutions are apparent, we will advocate for their adoption. Where solutions are less clear, we will propose research agendas needed to identify practical answers. The policy solutions are all expected to be difficult and will require considerable sustained funding and attention. In many cases, the solutions may be as much political as they are scientific. We encourage others engaged in the health security policy space to join us in seeking practical policy and operational solutions to the considerable challenges associated with a severe pandemic.