NTI Paper
NOVEMBER 2021

Strengthening Global Systems
to Prevent and Respond to
High-Consequence Biological Threats
Results from the 2021 Tabletop Exercise Conducted inPartnership with the Munich Security Conference
SUMMARYIn March 2021, NTI partnered with the Munich Security Conference toconduct a tabletop exercise on reducing high-consequence biological threats.
The exercise examined gaps in national and international biosecurity andpandemic preparedness architectures—exploring opportunities to improve
prevention and response capabilities for high-consequence biologicalevents. This report summarizes the exercise scenario, key findings fromthe discussion, and actionable recommendations for the international
community.

Jaime M. Yassif, Ph.D.
Kevin P. O’Prey, Ph.D.
Christopher R. Isaac, M.Sc.

We are grateful to Open Philanthropy. The exercise and report would not have been possible without their generous support.

Copyright © 2021 Nuclear Threat Initiative

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The views expressed in this publication do not necessarily reflect those of the NTI Board of Directors or the institutions withwhich they are associated.

Contents
Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Foreword. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Executive Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
About the Exercise. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Summary of Exercise Discussion and Findings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Recommendations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Appendix A. Expert Contributors to Scenario Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Appendix B. Epidemiological Model Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
About the Authors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

AcknowledgmentsT

he authors gratefully acknowledge the support of those who were instrumental in the development
and execution of this senior-level tabletop exercise. First, we would like to thank our partners at theMunich Security Conference, who jointly hosted this exercise with NTI. We are also grateful to the exercise
participants whose valuable insights, expertise, and engagement were crucial to the success of this project.
We also thank Talus Analytics for developing the epidemiological model underpinning this exercise, ourexpert advisors who informed the design of the exercise scenario early in the process, and Long Story Shortfor producing the exercise videos.
At the Nuclear Threat Initiative (NTI), we would like to thank members of the project team, who were
instrumental to the success of this project. Dr. Andrew Hebbeler, who is now serving in government at theWhite House Office of Science and Technology Policy, jointly led the development and planning of thisexercise with Dr. Jaime M. Yassif. Dr. Kevin P. O’Prey facilitated the scenario-based exercise, in addition
to advising on exercise planning and jointly authoring this report. Christopher R. Isaac provided valuable
research assistance for this project, and Amanda Cogan was instrumental in organizing the exercise event.
From NTI’s Communications team, Rachel Staley Grant led the development of video production for thisexercise, and along with Mimi Hall, provided valuable comments on this manuscript and led the reportpublication process.
We are grateful to Open Philanthropy for their support for this project as part of their ongoing support ofour work to reduce Global Catastrophic Biological Risks.
Jaime M. Yassif, Ph.D.
Senior Fellow, Global Biological Policy and Programs, NTI
Kevin P. O’Prey, Ph.D.
Managing Partner, The Palisades Group, LLC
Christopher R. Isaac, M.Sc.
Program Assistant, Global Biological Policy and Programs, NTI

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

ForewordOver the past two years, the world has faced the devastating impact that a biological event can have onhuman health, economies, and political stability. As of this writing, the SARS-CoV-2 virus has infected
more than 250 million people, killed more than five million, and caused trillions of dollars in economic
losses. COVID-19 has revealed that national governments and the international community are woefully
unprepared to respond to pandemics—underscoring our shared vulnerability to future catastrophic
biological threats that could meet or exceed the severe consequences of the current pandemic.

Although national and global leaders are appropriately focused on the immediate demands of the
COVID-19 response, the international community cannot postpone implementing the steps necessary toprotect against future biological threats. This must include the recognition that while naturally emerging
pandemics continue to pose a significant threat, the next global catastrophe
could be caused by the deliberate misuse of the tools of modern biology orby a laboratory accident. Fundamentally, strengthening the preparednessof every nation to meet these challenges is a humanitarian imperative in the
Scientific and politicalcollective self-interest of the international community. Even the most preparedleaders must take boldnations will remain vulnerable as long as significant biosecurity and pandemic
preparedness gaps remain in countries around the world. We are only as safe as
action to safeguard theour weakest link.
global bioscience andbiotechnology researchand development
enterprise to ensurethat catastrophic
accidents or deliberate
misuse do not leadto the next global
pandemic.

The world has witnessed how global travel, trade, urbanization, andenvironmental degradation can fuel the emergence and spread of infectious
disease threats. However, the serious risks embedded in the very bioscience
research and technology advances that offer vital opportunities to counter theserisks remain less understood. Bioscience and biotechnology advances, while
offering tremendous potential benefits, also present opportunities for accidental
release or deliberate abuse of biological agents that could cause as much or more
harm than COVID-19. Scientific and political leaders must take bold action tosafeguard the global bioscience and biotechnology research and development
enterprise to ensure that catastrophic accidents or deliberate misuse do not leadto the next global pandemic.

To strengthen international capabilities to respond to the next pandemic,
national and global leaders must build stronger public health and medical
response capabilities that can scale to address very high-consequence biological events—potentially ordersof magnitude more severe than what we have experienced during the past two years. We cannot afford to bereactive. We must build our public health and medical systems to be anticipatory, responding energeticallyand proactively in the face of uncertainty—taking what humanitarian and crisis response communities
describe as a “no regrets” approach.

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

NTI recognizes the critical importance of strengthening the global biosecurity and pandemic preparedness
architecture. To that end, NTI is focused on catalyzing the development of stronger international biosecurity
and pandemic preparedness capabilities so the world is better able to prevent and respond to future biologicalrisks. To address important gaps in key areas, NTI is working with international partners:• To establish a new global biosecurity entity dedicated to reducing emerging biological risks that
can accompany certain technology advances. Its mission will be to reduce the risks of catastrophic
consequences due to accidents, inadvertent misuse, or deliberate abuse of bioscience andbiotechnology by promoting stronger global biosecurity norms and developing tools and incentives
to uphold them.
• To explore the possibility of establishing a new Joint Assessment Mechanism to investigate highconsequence biological events of unknown origin. This new mechanism would operate at the“seam” between existing mechanisms—including World Health Organization (WHO) outbreak
investigation capabilities and the United Nations Secretary-General’s Mechanism for investigating
alleged deliberate bioweapons use—thereby strengthening UN system capabilities to investigate
pandemic origins.
• To advocate for establishing a catalytic, multilateral financing mechanism for global health security
and pandemic preparedness. The goal is to accelerate sustainable biosecurity and pandemic
preparedness capacity-building in countries where resources are most needed.
To further examine these issues, NTI has partnered with the Munich Security Conference (MSC) overthe past three years to host annual tabletop exercises focused on reducing high-consequence biologicalthreats. NTI and MSC have jointly convened international leaders and experts to explore gaps in the global
biosecurity and pandemic preparedness architecture, and to identify opportunities to address urgent needs.
This report shares the lessons of our 2021 exercise.

Margaret A. Hamburg, M.D.
Interim Vice President, Global Biological Policy and Programs
Nuclear Threat Initiative

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

Executive SummaryIn March 2021, the Nuclear Threat Initiative (NTI) partnered with the Munich Security Conference (MSC)
to conduct a tabletop exercise on reducing high-consequence biological threats. Conducted virtually, theexercise examined gaps in national and international biosecurity and pandemic preparedness architecturesand explored opportunities to improve capabilities to prevent and respond to high-consequence biologicalevents. Participants included 19 senior leaders and experts from across Africa, the Americas, Asia, andEurope with decades of combined experience in public health, biotechnology industry, international
security, and philanthropy.
The exercise scenario portrayed a deadly, global pandemic involving an unusual strain of monkeypox virusthat emerged in the fictional nation of Brinia and spread globally over 18 months. Ultimately, the exercise
scenario revealed that the initial outbreak was caused by a terrorist attack using a pathogen engineeredin a laboratory with inadequate biosafety and biosecurity provisions and weak oversight. By the end of
the exercise, the fictional pandemic resulted in more than three billion cases and 270 million fatalities
worldwide.
Discussion among exercise participants led to the following key findings:• Weak global detection, assessment, and warning of pandemic risks. The international
community needs a more robust, transparent detection, evaluation, and early warning systemthat can rapidly communicate actionable information about pandemic risks.
• Gaps in national-level preparedness. National governments should improve preparedness bydeveloping national-level pandemic response plans built upon a coherent system of “triggers”
that prompt anticipatory action, despite uncertainty and near-term costs—in other words, on a“no-regrets” basis.
• Gaps in biological research governance. The international system for governing dual-use
biological research is neither prepared to meet today’s security requirements, nor is it ready forsignificantly expanded challenges in the future. There are risk reduction needs throughout thebioscience research and development life cycle.
• Insufficient financing of international preparedness for pandemics. Many countries aroundthe world lack financing to make essential national investments in pandemic preparedness.

To address these findings, the authors developed the following recommendations.
1

Bolster international systems for pandemic risk assessment, warning, and investigating outbreakorigins• The WHO should establish a graded, transparent, international public health alert system.
• The United Nations (UN) system should establish a new mechanism for investigating highconsequence biological events of unknown origin, which we refer to as a “Joint Assessment
Mechanism.” (More about the Joint Assessment Mechanism is found on page 22.)NTI Paper

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

2

Develop and institute national-level triggers for early, proactive pandemic response• National governments must adopt a “no-regrets” approach to pandemic response, taking
anticipatory action—as opposed to reacting to mounting case counts and fatalities, which arelagging indicators.
• To facilitate anticipatory action on a no-regrets basis, national governments should develop
national-level plans that define and incorporate “triggers” for responding to high-consequence
biological events. (More about “triggers” is found on page 17.)3

Establish an international entity dedicated to reducing emerging biological risks associated with
rapid technology advances• The international community should establish an entity dedicated to reducing the risk ofcatastrophic events due to accidents or deliberate abuse of bioscience and biotechnology.
• To meaningfully reduce risk, the entity should support interventions throughout the bioscienceand biotechnology research and development life cycle—from funding, through execution, and on
to publication or commercialization.

4

Develop a catalytic global health security fund to accelerate pandemic preparedness capacity
building in countries around the world• National leaders, development banks, philanthropic donors, and the private sector should
establish and resource a new financing mechanism to bolster global health security and pandemic
preparedness.
• The design and operations of the fund should be catalytic—incentivizing national governments toinvest in their own preparedness over the long term.

5

Establish a robust international process to tackle the challenge of supply chain resilience• The UN Secretary-General should convene a high-level panel to develop recommendations forcritical measures to bolster global supply chain resilience for medical and public health supplies.

This report is organized into three parts: the first is a description of the exercise design and scenario;
the second is a summary of the exercise discussions and related findings; and the third is a set ofrecommendations developed by the authors to address the identified gaps and requirements. NTI developed
these recommendations after the event concluded; participants were not involved in their development
and have not been asked to endorse them. The appendices provide a list of the experts who supported theexercise development process (Appendix A) as well as technical details about the epidemiological model(Appendix B) used to inform this fictional monkeypox pandemic scenario.

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

About the Exercise

I

n March 2021, NTI conducted a Tabletop Exercise on Reducing High-Consequence Biological Threats,
the third in a series of annual collaborations between NTI and the Munich Security Conference. The
exercise examined gaps in national and international biosecurity and pandemic preparedness architecturesand explored opportunities to improve capabilities to prevent and respond to high-consequence biologicalevents. The exercise included 19 senior leaders and experts from across Africa, the Americas, Asia, andEurope with decades of combined experience in public health, biotechnology industry, international
security, and philanthropy. (See the box on page 9 for the list of exercise participants.)

Exercise Scenario
Developed in consultation with technical andpolicy experts, the exercise scenario portrayeda deadly, global pandemic involving an unusual
strain of monkeypox virus that first emerges in thefictional country of Brinia and eventually spreads
globally. Later in the exercise, the scenario reveals
that the initial outbreak was caused by a terrorist
attack using a pathogen engineered in a laboratory
with inadequate biosafety and biosecurity
provisions and weak oversight. The exercise
scenario concludes with more than three billion
cases and 270 million fatalities globally. As part ofthe scenario development process, NTI conducteda virtual consultation with experts in December
2020. (See Appendix A for the list of participating
experts.)

The fictional exercise scenario unfolded in a series ofshort news videos that participants reacted to.

The exercise was designed for participants to:• Discuss requirements for international architectures related to science-based, early assessment ofemerging pandemic risks and timely international warning and alerts for potential pandemics.
• Explore conditions that should trigger national pandemic response actions and discuss strategies
and challenges for scaling public health interventions.
• Consider options to reduce biotechnology risks and strengthen oversight of dual-use bioscience
research.
• Explore opportunities to strengthen international financing mechanisms to bolster global healthsecurity preparedness.

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

2021 NTI-MUNICH SECURITY CONFERENCE TABLETOP EXERCISE PARTICIPANTS

EXERCISE CO-CHAIRS
Dr. Ernest J. Moniz
Co-Chair and CEO
Nuclear Threat Initiative
Former U.S. Secretary of Energy

Ambassador Wolfgang Ischinger
ChairmanMunich Security Conference

PARTICIPANTS
Mr. Arnaud Bernaert
Head, Health Security Solutions
SICPA

Ms. Angela Kane
Visiting Professor
Paris School of International Affairs (SciencesPo),
and Tsinghua University

Dr. Beth Cameron
Senior Director, Office of Global Health Security andBiodefense
U.S. National Security Council

Dr. Emily Leproust
CEO and Co-Founder
Twist Biosciences

Mr. Luc Debruyne
Strategic Advisor to the CEO
Coalition for Epidemic Preparedness

Dr. Elisabeth Leiss
Deputy Director of the Governance and Conflict
Division
German Corporation for International Cooperation(GIZ)

Dr. Ruxandra Draghia-Akli
Global HeadJohnson & Johnson Global Public Health R&D
Janssen Research & Development

Ms. Izumi Nakamitsu
Under-Secretary-General and High Representativefor Disarmament Affairs
United Nations Office for Disarmament Affairs

Dr. Chris Elias
President, Global Development Division
Bill & Melinda Gates Foundation

Dr. John Nkengasong
Director
Africa Centres for Disease Control and Prevention

Sir Jeremy Farrar
Director
Wellcome Trust

Sam Nunn
Founder and Co-Chair
Nuclear Threat Initiative
Former U.S. Senator

Dr. George Gao
Director-General, Chinese Center for Disease
Control and Prevention (China CDC)
Vice President, the National Natural Science
Foundation of China (NSFC)
Director and Professor, CAS Key Laboratory of
Pathogenic Microbiology and Immunology, Instituteof Microbiology, Chinese Academy of Sciences
Dean, Medical School, University of Chinese
Academy of Sciences

Dr. Michael Ryan
Executive Director
WHO Health Emergencies Programme
Dr. Joy St. John
Executive Director
CARPHA
Dr. Petra Wicklandt
Head of Corporate Affairs
Merck KGaA

Dr. Margaret (Peggy) A. Hamburg
Interim Vice President
Global Biological Policy and Programs, Nuclear
Threat Initiative
Former Commissioner of the U.S. Food and Drug
Administration

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

The discussion was organized into three sequential “moves” corresponding with scenario developments,
followed by a roundtable discussion of broader biosecurity and pandemic preparedness issues. The stepby-step approach to revealing scenario developments reflected the limitations of information available toreal-world decision makers, as well as the resulting uncertainty associated with a pandemic of unknown
origin (see Figure 1).
Figure 1. Scenario Design Summary

MOVE 1
Scenario

Key Issues

ATTACKMay 15, 2022

• Monkeypox outbreak in Brinia
1,421 cases/4 deaths• International alert & warning
systems

June 5, 2022

• No international warnings oradvisories• Benefits of & need for early risk
assessment

MOVE 2January 10,
2023

Scenario

Key Issues• 83 countries affected
70M cases/1.3M deaths• Benefits of pre-determinedtriggers for national response• Monkeypox engineered to be
vaccine-resistant• International supply chain
challenges• National responses: effects ofearly action• International supply chain
challenges

May 10, 2023

MOVE 3
Scenario

Key Issues• 480M cases/27M deaths• Biosecurity and governance ofdual-use bioscience research• Revelation of terror grouporigins—infiltration of civilian
bio lab

ROUNDTABLE
December 1,
2023

Scenario

Key Issues• 3.2B cases/271M deaths• International financing for
pandemic preparedness• Global differences in national
responses contribute tosignificantly variable outcomes

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

Move 1 (occurring on June 5, 2022, in scenario time) starts with an unusual outbreak of monkeypox in Brinia(population 250 million), with reports of 1,421 cases and four fatalities. There is no immediate evidence ofinternational spread, but the outbreak takes place during a national holiday with extensive domestic andinternational travel by Brinians. Because monkeypox is not naturally found in Brinia, local and international
experts consider this outbreak to be unusual. The Brinian government welcomes international outbreak
investigations and requests medical support from the WHO. Genome sequencing of monkeypox patient
samples reveals that the strain in Brinia contains mutations that make it resistant to existing vaccines.
The discussion that followed considered how the international system is postured to analyze initial indicatorsof pandemic risk and to communicate appropriate warnings.
Move 2 (January 10, 2023) occurs six months later, at which point the virus has spread to 83 countries with70 million reported cases, causing more than 1.3 million fatalities. With no known effective therapies or
vaccines, countries have had to rely principally on non-pharmaceutical interventions (NPIs) to mitigate theimpacts of the pandemic. Highlighting significantly different national outcomes in managing the pandemic,
some governments, including the fictional Republic of Dranma, promptly adopted aggressive measures
to slow virus transmission by shutting down mass gatherings, imposing social-distancing measures, andimplementing mask mandates. These countries have also established large-scale testing and contact-tracing
operations and scaled-up their health care systems to support anticipated growing case numbers. By
contrast, the scenario depicts another group of countries, including fictional Cardus, that have prioritizedkeeping their economies open, undertaking little-to-no NPIs, and downplaying the virus and its potential
impacts. These countries have experienced much worse outcomes in terms of illness and mortality (Figure2) than those that responded early and energetically. As Figure 3 shows, Dranma experienced far fewercases and fatalities than Cardus.
Participant discussion in Move 2 focused on exploring the conditions that should trigger national pandemic
response actions and discussing strategies and challenges for scaling public health interventions.
Figure 2. Cardus vs. Dranma: Cumulative Deaths
MOVE 2MOVE 1

Number of Deaths

100,000,000

1,000,000

10,000100

0Jun 2022

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Dec 2022

Mar 2023

Jun 2023

Sep 2023

Cardus Deaths

Cardus Projected Deaths

Dranma Deaths

Dranma Projected Deaths11

Dec 2023

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

Figure 3. Cardus vs. Dranma: Cumulative Cases
MOVE 1MOVE 2

Number of Cases

100,000,000

1,000,000

10,000100

0Jun 2022

Sep 2022

Dec 2022

Mar 2023

Jun 2023

Sep 2023

Cardus Cases

Cardus Projected Cases

Dranma Cases

Dranma Projected Cases

Dec 2023

Move 3 (May 10, 2023) occurred 12 months after the initial outbreak, with more than 480 million cases and27 million fatalities globally (Figure 4). At this stage, participants learn that the pandemic was caused by aregional bio-terror attack that far exceeded the perpetrators’ goals.
Figure 4. Global Cumulative Cases and Deaths
3,500,000,000

MOVE 1MOVE 2MOVE 3

ROUNDTABLE

3,000,000,000

Number of People

2,500,000,000
2,000,000,000
1,500,000,000
1,000,000,000
500,000,000
0Jun 2022

Sep 2022

Dec 2022

Mar 2023

Global Cumulative Cases

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Jun 2023

Sep 2023

Dec 2023

Total Deaths

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological ThreatsSpecifically, Brinian intelligence reveals that the engineered monkeypox virus was developed illicitly at
the fictional country of Arnica’s leading institute for virology. Arnica (population 75 million) has a historyof conflict with neighboring Brinia (see map in Figure 5). An independent Arnican terrorist group—the
SPA—had worked with sympathetic laboratory scientists toengineer a highly contagious, deadly pathogen and disperse
it at crowded train stations in Brinia during the national
Figure 5. Map of the Fictional
holiday, when much of the population was travellingCountry of Brinia, the Geographic
domestically and internationally.
Origin of the Outbreak
The SPA had exploited the Arnican government’s weakoversight of its bioscience research laboratories. SPA
sympathizers working in Arnica’s leading virology instituteused publicly available scientific publications to guide theirwork to modify the monkeypox virus to make it moretransmissible and resistant to currently available vaccines.
The discussion in Move 3 focused on governance of dualuse bioscience research as well as current weaknesses inbiosafety and biosecurity systems that exacerbate biologicalrisks.

BRINIA

ARNICAThe final phase of the exercise was a roundtable discussionthat considered disparities in public health preparedness
around the globe and the resulting need for more effective
financing mechanisms to accelerate pandemic preparedness capacity building. Recognizing that pandemic
preparedness requires costly investments that lower- and lower-middle income countries cannot afford to
make, participants were asked to discuss strategies to catalyze these investments in sustainable ways.

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Summary of Exercise Discussion andFindings

T

he discussions throughout the tabletop exercise generated a wide range of valuable insights and key
findings. Most significantly, exercise participants agreed that, notwithstanding improvements following
the global response to COVID-19, the international system of pandemic detection, analysis, warning, andresponse is woefully inadequate to address current and anticipated future challenges.
Exercise participants agreed that gaps in the international biosecurity and pandemic preparedness
architecture are extensive and fundamental, undermining the ability of the international community
to mount effective responses to future biological events—and they noted that robust preparedness will
require fundamental transformation across a number of fronts. Given the inherent latency in acquisition ofdefinitive data on pandemic threats—e.g., geographic distribution, transmission rates, and lethality—andthe very serious consequences of delay in pandemic response, participants observed that the international
system and national governments must be transformed to emphasize pre-determined “no-regrets”
anticipatory actions. Such a system requires significant improvements in the international community’s
ability to detect, assess, and warn about pandemic threats as well as to develop proactive, national-level
response plans and decision-making bodies. They agreed that the international community also must
bolster its system of governance for dual-use life-science research, and they concluded that governments
globally are severely underinvesting in pandemic preparedness—especially in low- and lower-middle
income countries. These consensus findings frame the more detailed conclusions discussed below.
FINDING 1

The international community needs a more robust, transparent
detection, evaluation, and early warning system that can rapidly
communicate actionable warnings about pandemic risks.
Exercise participants found that the world continues to lack a coherent system for pandemic detection andassessment that would be effective across the full range of plausible scenarios. In this exercise, the scenario
arguably depicted a “best case” where the country of origin reported what it knew to the WHO in a timely
manner and welcomed international investigation. Yet even in this case, exercise participants expressed
concern that it would be extremely challenging to discern warning signals early enough to contain or atleast mitigate the effects of the initial outbreak.
Consequently, several participants stressed that the international community requires a more coordinatedinternational biosurveillance network, which also incorporates pathogen genome sequencing. In scrutinizing
disease outbreaks for pandemic potential, exercise participants identified a number of key indicators for aneffective risk assessment system based on biosurveillance data.
Participants stressed that the most important indicators for analyzing the pandemic potential of an
outbreak are its epidemiology and the geographic distribution of cases. A novel virus that is assessed to be

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threatshighly virulent and transmissible—either based on direct epidemiological observations or other evidencebased predictions—will warrant significant attention. Analyzing additional virus characteristics will also
be important. For example, is the virus changing and/or is it different from previously detected variants?
One participant observed that the number of fatalities would not be a goodmeasure to track in the early period of a pandemic because it is a lagging
indicator at a time of exponential growth in cases.
Participants also suggested that considering the social, political, and economic
context of the country of origin or initial detection could be valuable for risk
assessment. Key factors include the degree of societal openness of the country
and the extent of international travel across its borders—both features that
could contribute to faster spread. Another consideration is the strength ofthe country’s public health system and whether the population is reducing
the risk of spread by using NPIs and avoiding mass gatherings.

“We face thesimultaneous challengeof responding to thispandemic and preparing
for the next one. Theinternational community
has an opportunity, if not
an obligation, to improve
the situation.”In the sequence of events after detection and analysis, the next step is warning.
All participants agreed that the principal means of international pandemic risk
warning now in place—the WHO Director General’s declaration of a Public
Health Emergency of International Concern (PHEIC)—requires significant—Exercise Participantreform. Among the shortfalls they identified in the current PHEIC approachis that it is a binary tool for a world where pandemic risks are characterized
by different levels of risk that evolve over time. The current PHEIC approach
potentially lumps risks like a limited regional Ebola outbreak with a globallycatastrophic biological event. Both are concerning, but to very different degrees, and they warrant different
responses. The binary nature of the PHEIC also unintentionally creates incentives to delay warnings. In
effect, if analysts and decision makers only have two choices, they are likely to err on the side of certainty
before activating an international alert system.
Participants stressed that a graded pandemic warning system—analogous to graded systems used for
hurricanes and other natural disasters—would arguably provide a more flexible, informative, and actionablesystem for communicating risk. Under the current International Health Regulations (IHR 2005), the WHO
could be empowered to provide more detailed risk assessments to member states. One participant notedthat formally shifting the WHO PHEIC to a graded system might require a change to the IHR, which could
pose significant political challenges.
Exercise participants observed that regardless of the particular institutional arrangements chosen forinternational systems of pandemic detection, analysis, and warning, these systems must be transparent.
In particular, deliberations that currently occur behind closed doors—the WHO Emergency Committee,
for example—would benefit if, at a minimum, an outside expert group could analyze the data and reachconclusions in parallel. Arguably, this would help validate and lend independent weight to official findings,
or could challenge findings if they are inconsistent with available evidence.1

1

For an excellent discussion of reported politicization of PHEIC deliberations and decisions, see Clare Wenham, Alexandra Phelan, Mark
Eccleston-Turner, and Sam Halabi, “Reforming the Declaration Power for Global Health Emergencies,” International Law Impact andInfectious Disease (ILIAID) Consortium IHR Reform White Paper Series (1), (November 2020): 8.

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

Evaluating Outbreak Origins
Participants noted that biological incidents of unknown original fall into a gap in the UN system. The
WHO, as one participant highlighted, is the outbreak equivalent of a firefighter, not a police officer; theorganization is best suited to public health and medical response, not security investigations. In cases wherean outbreak is deliberately caused, a security investigation by the UN Secretary-General’s Mechanism(UNSGM) would be appropriate. However, the means by which the WHO and the UN Secretary-General
operate in parallel, if not in coordination, are still unclear. More problematic still are those cases where
the origin of an incident is unclear or suspicious. In these cases, the respective roles of the UN SecretaryGeneral and WHO must be clearly defined.2
Participants discussed additional international political challenges that could pose obstacles to effective
investigation of an outbreak. First, the international community requires cooperation and transparency
from the putative country of origin. Second, although the Secretary-General has the authority to use
its investigative mechanism in response to a request from any member state, the mechanism has neverbeen used to investigate a biological incident, and tensions among UN member states could cause delays.
Similarly, objections by any of the WHO principal member state donors could hamper the organization’s
effectiveness in coordinating prompt detection and assessment.
FINDING 2

Governments should improve preparedness by developing nationallevel pandemic response plans built upon a coherent system of“triggers” that prompt anticipatory action on a “no-regrets” basis.

“It will be chaotic andfrightening, but you
can’t wait until you havecertainty. You have to act
with no regrets.”

Tabletop exercise participants agreed that the exercise scenario and the larger
lessons from the global COVID-19 response highlight the need to establish
national response plans with a series of planning “triggers,” or thresholdconditions, that ensure anticipatory steps early in a potential pandemic.
Both the exercise scenario and the COVID-19 response demonstrate thatearly actions by national governments have significant, positive impacts
in managing the impact of the disease. Because the nature of exponential
disease transmission severely punishes even modest delays, slow responses
by national governments lead to higher caseloads, worse mortality rates, andpotentially even the collapse of the public health and medical system.

—Exercise Participant

The Benefits of Early Action
One participant observed that the exercise outcomes were consistent withnational performance during the COVID-19 response; governments that

2

The UN Secretary-General’s Mechanism and the need for a Joint Assessment Mechanism were key discussion points in the 2019 and 2020
NTI-MSC tabletop exercises. Reports from these exercises are available at nti.org.

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

responded early and energetically to pandemic warnings were much more successful in protecting their
populations. As is widely recognized, a number of wealthier countries with strong public health systems
were not proactive and timely in their responses and therefore experienced significantly worse outcomesthan those nations that are less wealthy but responded more proactively.

What Is a Trigger?
In national pandemic response plans, specific readiness measures would be “triggered” based on factors
related to the potential severity of the outbreak, expected delays in situational awareness, and the time it
would take to implement response measures and see results.
Participants stressed that national-level decision makers must build trigger-based plans that emphasize
a “no-regrets” bias toward early action. Although there is inevitably a risk of false-alarm responses,
participants deemed the risk of delay as far more consequential. Action, one participant argued, must be
the “default pathway” because “you will not have the luxury of waiting for certainty.”
Although triggered actions would vary depending upon the particularneeds of the country, in most cases the goals are the same: slow the spreadof disease to buy time and flatten the epidemiological curve, while usingthat time to scale up public health and medical systems to keep up withgrowing caseloads and save lives. NPIs such as mask mandates and ceasing
mass gatherings were deemed to be critical for blocking chains of diseasetransmission. Participants generally did not endorse travel restrictions suchas border closures, but travel health screening measures were viewed as
valuable.
With the time bought by NPIs, participants argued for scaling up various
capacities. The highest priority is implementing testing at scale and increasing
health system capacity in terms of facilities and personnel. In addition,nations should ramp up production of the range of critical supplies that
could otherwise cause bottlenecks in response operations, including masks,
personal protective equipment (PPE) for health workers, testing reagents,
oxygen tanks, and ventilators.

“We want to focus thetriggers on a large healthresponse so we can findthe disease, understandit, slow the spread, andeventually understandwhat it is and how to stopit from moving.”—Exercise Participant

The triggers should not be limited just to actions; they should address institutional relationships as well.
Indeed, a number of participants stressed that the whole-of-government decision-making process fornational-level pandemic response must be planned and exercised as soon as possible, before the next
pandemic. Several participants argued that most national governments have too many “silos” of decision
making that must be swiftly integrated for a successful pandemic response. An effective, “no-regrets”
national response will demand that the whole-of-government engage early, so internal bureaucratic hurdles
do not cause critical delays.

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Bolstering Pandemic Supply Chain Resilience
All participants agreed that bolstering supply-chain resilience would be critical in future pandemic responses,
but they differed on how to address the challenge. In particular, a debate ensued about whether the rightapproach for ensuring the availability of critical items is stockpiling or maintaining “warm” production
capacity,3 or a mixture of both. For those items with long shelf lives—such as masks and other PPE—someparticipants argued that it is prudent for national governments and international institutions to stockpile.
Others argued that governments and/or international organizations should provide incentives to keep
dual-use supply lines open or at least, “warm”—which could, for example, assist with large-scale ventilator
production during an international public health emergency. An even more advanced scientific andengineering solution, where possible, would be to develop platform technologies—tools to rapidly develop
diagnostics, vaccines, and other medical countermeasures for the wide range of pathogens with pandemic
potential.
One participant offered a related vaccine supply recommendation that strikes a balance between national
stockpiling and global coordination: selecting and empowering leading governments in each of the globe’s
regions. In particular, this participant argued for the creation of a global network of small-population
countries that would be charged with manufacturing at scale for their respective regions.4 Such an approach
would require regional agreement and cooperative financing to build the capabilities in the selected
countries.
FINDING 3

The international system for governing dual-use biological researchis neither prepared to meet today’s security requirements, nor isit ready for significantly expanded challenges in the future. There
are risk reduction needs throughout the bioscience research anddevelopment life cycle.
Exercise participants discussed the importance of strengthening biosecurity for bioscience research anddevelopment. Emerging biological risks associated with rapid technology advances are not new, butparticipants recognized that the COVID-19 pandemic has exacerbated these risks. They pointed out thatthe international community should expect to see a rapid expansion of high-containment laboratories(biosafety level 3 and 4 labs) as a number of countries expand their bioscience research capabilities andengage in more dual-use research on SARS-CoV-2 and other pathogens with pandemic potential.
Participants agreed that, although it is essential to avoid restricting legitimate biological research, it also
is critically important to incorporate stronger biosafety and biosecurity measures into bioscience research3

A warm production capacity would involve maintaining the production line, human expertise, and supply lines for a product even if there isno current market demand.

4

In the case of vaccines, for example, these countries would be expected to provide for their own populations first. But because their
populations are small relative to their production capacity, they would be able to turn to support the needs of their region in short order.

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and development processes—from project design and funding, through research execution, and on to
publication or technology commercialization.

Funders
At the beginning of the research and development life cycle, government, philanthropic, and industry
funders can play a role in early review of proposed research projects, thereby creating a stronger framework
for biosecurity and responsible research. Participants argued that these activities will need to encompass bothpublic and private funders, while recognizing that incorporating the latter may be particularly challenging.
During this discussion, several participants argued that the funders cannot
be the only arbiter and that implementing a biosecurity review as part of theevaluation process for funding new projects will need to be part of a morecomprehensive solution.
“Responsible stewardship

Institutional Oversight
Institutional oversight—addressing both academic and industrial research
institutions—is an important step in the middle of the research anddevelopment life cycle. Some participants argued that in the industry context,
boards of directors should take responsibility for biosecurity much as they
are increasingly addressing cybersecurity as a corporate governance issue.
Participants acknowledged that biosecurity measures would likely add costs
to operations—which may be considered high or even prohibitive for small
biotechnology companies. However, at least one participant argued that thedownside risk for a company involved in a biosecurity incident warrants thiskind of executive-level attention and investment.
Some participants also argued that education can play an important role inbolstering private sector biosecurity, observing that many in the sector are
ignorant of the security risks.

of biotechnology andbiomedical research is
not going to be solved
at any one institution.
It will require a
multifaceted approachthat includes norms
and standards, national
regulations, and regional
strategies. Companies,
professional societies,
funders, and publishers
can all play an importantrole.”—Exercise Participant

Providers of Goods and Services

The middle of the bioscience research and development life cycle also
involves numerous private-sector entities, including providers of goods
and services. For example, a number of companies provide DNA synthesis
services to research laboratories. Exercise participants noted that approximately 80 percent of DNA
providers are members of the International Gene Synthesis Consortium, which screens customers andDNA order sequences to prevent the building blocks of dangerous pathogens from falling into the handsof malicious actors.5 However, screening is costly, time-consuming, and requires human expertise, so non5

Formed in 2009, International Gene Synthesis Consortium (IGSC) members screen synthetic gene orders to identify regulated pathogen
sequences and other potentially dangerous sequences. By screening the sequences of ordered DNA fragments and vetting customers, IGSC
members help to ensure that researchers and the synthetic biology community realize the many benefits of gene synthesis technology while
minimizing risk. See genesynthesisconsortium.org.

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participants have an economic advantage over Consortium members. A sustainable system must include
either incentives to participate or other ways to drive toward 100 percent participation.
Benchtop synthesis devices—smaller machines that individual research facilities can use to print DNA
locally, as opposed to ordering from centralized DNA providers—create additional challenges. Participants
observed that the entrance of benchtop DNA synthesis machines into the market poses greater risks ofdangerous research with no traceability if effective biosecurity provisions are not incorporated.

International Efforts
All participants agreed that at the international level, the system for biosecurity and biosafety in bioscience
research is fragmented, although they offered a range of possible remedies.
Recognizing that no comprehensive international solution exists, several participants argued for establishinga new entity that would work with a wide range of international stakeholders to develop biosecurity norms
and standards and develop tools to promote compliance. It could provide both general biosecurity education
as well as targeted technical assistance to companies, governments, and/or regional organizations. Several
participants pointed to an example of a successful normative entity in the World Institute for Nuclear
Security,6 which performs similar functions in the nuclear security field. At least one participant stressed
the importance of bolstering existing mechanisms and institutions, as opposed to creating new ones.
Participants also discussed various biosecurity approaches at national and regional levels. Short of unified
international guidelines, one participant argued that opportunities exist for international approaches
to encourage national-level biosecurity regulation. In particular, this participant observed that existing
international agreements or frameworks—such as the Biological Weapons Convention (BWC)—might
facilitate or even require member nation adoption of biosecurity legislation. Others pointed to the promiseof progress at the regional level. Described by one participant as a “sea change,” Africa, the Caribbean, andEurope all have developed or are developing regional biosecurity frameworks. For example, the Africa
Centers for Disease Control (CDC) is developing a continent-wide biosafety and biosecurity framework.
For dual-use research, Africa CDC is proposing a legal framework to establish a requirement for all
institutions handling high-risk materials to conduct risk assessment and install mitigation measures anda requirement for all institutions and labs to report their cases of Dual-Use Research of Concern (DURC)
to the government. The European Union has a dual-use research framework that is designed to facilitate
information exchange. The Caribbean Public Health Agency has developed and implemented an ethicalframework through a network of research ethics committees and is working to strengthen standards forbioscience labs.

6

See https://wins.org/.

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

FINDING 4

Many countries around the world currently lack financing to makeessential national investments in pandemic preparedness.
Exercise participants discussed the need for substantially increased international financing for pandemic
preparedness. Although they agreed that faulty policy choices and leadership failures had contributed
profoundly to poor national outcomes in the COVID-19 response, they also agreed that pre-pandemic
investments in preparedness are essential. Surveying the global landscape of public health spending, one
participant stressed that “we have been trying to stop a tsunami with ateaspoon.” Participants noted that the challenge of financing is aggravatedby significant problems of international inequity, recognizing that not all
countries have the resources to make these investments. Because pandemics“We have been trying
do not respect borders, participants agreed that a failure to bolster
to stop a tsunami with apreparedness across all countries would inevitably pose significant risks for7
teaspoon.”even the best prepared nations.
Participants highlighted the need to create a sustainable financing
mechanism for improving pandemic preparedness. The new mechanism
should incentivize recipient governments to develop priorities and plans fordomestic pandemic preparedness capacity building and to budget for these
activities on an ongoing basis.

—Exercise ParticipantParticipants argued for creating a single pot of funding with real executive authority over its disposition.
At least one participant stressed that the funding should come from a larger cross-section of the global
community than the limited number of countries that currently contribute. Another participant highlighted
the role of the private sector as a contributor, noting that the COVID vaccine market will exceed $150
billion in 2021. A small fraction of returns reinvested by industry would make a difference.

7

According to the UN, approximately 70 countries worldwide have been identified as “aid-dependent.” Countries like Liberia, South Sudan,
and Tuvalu depend upon external financing for more than 50 percent of their GDP. See “Are Developing Countries Getting the COVID-19
Funding They Need?” World Economic Forum, weforum.org.

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Recommendations

N

TI developed the following recommendations based on key findings from the exercise, discussed
above. These recommendations were developed after the exercise and do not necessarily reflect theviews of participants.
1

Bolster International Systems for Assessing Pandemic Risk, Issuing Warnings,
and Investigating Outbreak Origins

The NTI-MSC tabletop exercise and other studies have made a compelling case that a radically strengthened
global biosurveillance system is needed. However, data gathering and analytical elements are only part of
the task of prompt and effective pandemic response; risk evaluation, warning, and assessment of pandemic
origins also are critical for success.

The WHO must establish a graded, transparent, international public-health alert system.
• The WHO must upgrade the PHEIC system to provide more actionable alerts and warnings. The
system should include graded or incremental thresholds with clear specification of different levelsof risk supported by data, to allow for prompt decisions at the national level. Risk gradations should
be built explicitly on thresholds of pandemic potential—i.e., the potential of a disease outbreak to
spread globally and yield high case counts—as well as estimated severity, such as case fatality rate.
• If reforming the PHEIC system proves too difficult, given the politics of changing the IHRs, theWHO should establish a graded alert system to complement its current PHEIC tool.
• Either way, the criteria for the graded alert system should be public and fully transparent, along withany epidemiological data used to make a determination. Transparency of data and criteria will allow
independent assessment and vetting by other experts and organizations.

The UN system should establish a new Joint Assessment Mechanism to investigate
high-consequence biological events of unknown origin.
• The experience of SARS-CoV-2’s emergence demonstrates the importance of early international
investigation to aid the public health and medical response, to minimize unproductive fingerpointing, and to clearly establish an outbreak’s origin so that future outbreaks might be better
mitigated or even prevented.
• In addition to bolstering existing capabilities to conduct international public health investigations,a new Joint Assessment Mechanism is needed. This mechanism would use transparent, evidencebased approaches to investigate events of unknown, or even suspicious, origin. It would address
gaps between existing mechanisms—specifically the WHO outbreak investigation capabilities andthe United Nations Secretary-General’s Mechanism—while also incorporating and building uponthese existing systems.

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats• To ensure its legitimacy and effectiveness, UN member states should establish the authority forthe new mechanism through a vote at the UN General Assembly, with support from a broadinternational coalition of member states.
• The mechanism should be based within the UN Secretary-General’s office and under its authority.
• The Joint Assessment Mechanism must possess significant analytical and investigatory capabilities
and expertise, and make use of advanced biotechnology and bioinformatics tools.
2

Develop and Institute National-Level Triggers for Early, Proactive Pandemic
Response

Success in preventing or mitigating the effects of future pandemics will depend fundamentally on actions at
the national level. Although international institutions can provide timely warnings, advice, and coordination,
the power of national sovereignty means that the choices made by individual nations may have the mostdecisive impacts—both positive and negative. Moreover, the significant variability in effectiveness ofnational responses to COVID-19 demonstrates that public health and medical capacity alone is not a goodpredictor of pandemic response performance. Rather, early decisive action has been the main determinant
by which countries have managed their COVID-19 outbreaks most effectively.

National governments must adopt a “no-regrets” approach to pandemic response,
taking anticipatory action—as opposed to reacting to mounting case counts andfatalities, which are lagging indicators.
• Simply put, national governments and their leaders must err on the side of taking early action.
Recognizing that situational awareness of pandemic threats lags behind on-the-ground reality,
national leaders cannot wait for cases or fatalities to accumulate before responding. If there isa significant chance that the outbreak could turn into a pandemic, national leaders should lean
forward to scale up response efforts and capabilities.

To facilitate anticipatory action on a “no regrets” basis, national governments should
develop national-level plans that incorporate “triggers” for responding to highconsequence biological events.
• Triggered national-level pandemic response actions should support the strategy of flattening theepidemiological curve while rapidly scaling up health system capacity to prevent collapse in theface of growing caseloads. Triggered actions should serve three major goals: slowing pathogentransmission, saving lives, and improving situational awareness about the pathogen’s spread toenable effective targeting of resources. Triggered actions should include a range of NPIs, including
proactive social distancing and mask-wearing guidelines; large-scale testing and contact tracing;large-scale production of PPE and medical equipment; expansion of the pool of deployable medical
personnel and space to treat patients; and comprehensive risk communication.
• National-level triggers should include adjustments to institutional relationships and decision making
processes to facilitate rapid, whole-of-government response to emerging pandemic threats. Decision
making bodies with whole-of-government authorities and information should be stood-up early,

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and bureaucratic stovepipes that hamper information-sharing should be eliminated. Additionally,
relevant waivers, emergency declarations, clarifications of authorities, and legal determinations
should be identified for each phase of these triggers.
• National governments should codify triggers in plans that are routinely exercised, and the results
should be systematically evaluated to identify and implement corrective actions.
• The WHO should issue guidance that encourages or requires national governments to develop
national-level pandemic response triggers that are pathogen-agnostic and that scale up acrossmultiple levels with escalating pandemic risk.
3

Establish an International Entity Dedicated to Reducing Emerging Biological
Risks Associated with Rapid Technology Advances

Bioscience advances offer significant promise for the future, but they also pose risks of accidents or deliberate
misuse. Despite this concern, no international entity has a specific mandate to strengthen biosecurity andbioscience governance and to reduce emerging biological risks associated with technology advances.

The international community should establish an entity dedicated to reducing therisk of catastrophic events due to accidents or deliberate abuse of bioscience andbiotechnology.
• A UN agency or credible non-governmental institution should partner with experts from thescientific, philanthropic, security, and public health communities to create an international entity
dedicated to identifying and reducing emerging biological risks associated with technology
advances.
• The mission of this entity should be to strengthen global biosecurity norms and to develop tools andincentives to support adherence.
• The entity should be agile, innovative, and free to engage with a diverse range of stakeholders—
including industry, academia, and governments—to keep up with rapid bioscience advances andquickly develop effective approaches to address emerging risks. It should work in close coordination
with the Biological Weapons Convention, the WHO, and other international institutions.

To meaningfully reduce risk, the entity should support interventions throughout thebioscience and biotechnology research and development life cycle—from funding,through execution, and on to publication or commercialization. It should:• Support comprehensive and systematic DNA synthesis screening to prevent the building-blocks ofdangerous pathogens from falling into the hands of malicious actors. The new entity should support
more effective and comprehensive screening internationally, while also reducing risks associatedwith benchtop synthesis.
• Support the development of biosecurity standards for use by bioscience funders, who are uniquely
positioned to incentivize incorporation of biosecurity measures in grant or investment proposals.
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funders will support work that lacks important safeguards or is otherwise risky from a biosecurity
perspective.
• Guide universities and industry in developing effective approaches to strengthen oversight of dualuse bioscience research conducted within their laboratories.
• Support effective pre-publication biosecurity review. The entity could collaborate with editors andpublishers to improve biosecurity review of manuscripts and reduce the risks of public release of
information hazards (i.e., information that may increase risks of intentional misuse of bioscienceknowledge and biotechnology capabilities).
4

Develop a Catalytic Global Health Security Fund to Accelerate Pandemic
Preparedness Capacity Building in Countries around the WorldThe COVID-19 pandemic has exacerbated inequalities in international pandemic preparedness.8 Before thepandemic, experts assessed the gap in preparedness financing for low- and lower-middle income countries
to be approximately US$4.5 billion per year; a gap that has only grown since that time.9 The G20 High Level
Panel concluded that governments must dedicate at least US$75 billion over the next five years to financepandemic prevention and preparedness. A new, catalytic financing mechanism that is able to draw together
resources from a wide variety of sources would transform the global system, driving resources and attention
to the countries that need it most, and addressing critical gaps in the global health security architecture. 10

National leaders, development banks, philanthropic donors and the private sector
should establish and resource a new financing mechanism to bolster global healthsecurity and pandemic preparedness.
• This mechanism must mobilize at least US$10 billion annually over the next 10 years. The
mechanism should be oriented toward countries with the greatest need and be based on clear
metrics through rigorous assessment, such as the Joint External Evaluation and other resources likethe Global Health Security Index.
• This new financing mechanism should catalyze investments across sectors, drawing in funding fromgovernments, multilateral organizations, non-governmental organizations, private sector donors,
philanthropies, and individual donors.
• The funds should be disbursed transparently, driving resources to eligible countries to accelerate
progress toward specific, measurable pandemic preparedness benchmarks.

8

See, for example, Second Report on Progress, Prepared by the Independent Panel for Pandemic Preparedness and Response for the WHO
Executive Board, January 2021, pp. 5–6.

9

Financing Pandemic Preparedness and Response, Background Paper 14, Independent Panel for Pandemic Preparedness and Response, May
2021, p. 16.

10

See Pandemic Action Network Policy Brief, A New Multilateral Financing Mechanism for Global Health Security and Pandemic Preparedness,
August 2021, https://pandemicactionnetwork.org/wp-content/uploads/2021/08/A-New-Multilateral-Financing-Mechanism-for-GlobalHealth-Security-and-Pandemic-Preparedness.pdf. NTI strongly supports the additional recommendations and priorities laid out in thisbrief, which align with and support recommendations made in this paper.

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The design and operations of the fund should be catalytic, incentivizing national
governments to invest in their own preparedness over the long term.
• Loans and grants through the mechanism should be managed within a country’s national budget toincrease accountability, incentivize domestic resource mobilization, and promote a sustainable way
to shift accounting lines away from donor balance sheets to national budgets.
• To overcome the problem of dependence upon assistance, the mechanism should set various matchlevels by recipients, adjusted for their unique needs and means.
• The mechanism should complement existing mechanisms, such as the WHO Contingency Fund for
Emergencies and other funding available through the UN and the World Bank.
• Funds disbursed should prioritize preparedness activities, strengthening countries’ long-term
capacity and ensuring that preparedness remains a political and budget priority.
5

Establish a Robust International Process to Tackle the Challenge of Supply
Chain ResilienceAs highlighted by exercise participants, the COVID pandemic has revealed significant weaknesses in global
supply chains for critical medical and public health supplies. Robust systems for ensuring availability of
PPE, testing supplies, and biomedical equipment are an international public good, which will be critical
for responding to future pandemics. Achieving this goal will require energetic, focused planning andcoordination, which must take place before the urgent need arises. To be effective, such an initiative should
build upon lessons learned from the efforts of the UN COVID-19 Supply Chain Task Force and the Accessto COVID-19 Tools Accelerator.

The UN Secretary-General should convene a high-level panel to develop
recommendations for critical measures to bolster global supply chain resilience for
medical and public health supplies, including:• Developing more robust distributed production capabilities, which can provide needed supplies
across the globe,• Facilitating supply distribution, with a focus on transportation resources and pre-designatedsupplier-distributor-recipient relationships,• Focused support on improving capabilities to deliver supplies over the “last mile” in developing
countries.

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Appendix A. Expert Contributors to Scenario
Development
NTI convened a diverse group of experts in December 2020 to advise on the tabletop exercise scenario.
These experts participated as individuals—not as representatives of their respective organizations—andthey do not necessarily endorse the recommendations in this report.
Dr. Hillary Carter
Senior Advisor in the Countering Weapons of Mass
Destruction Office
Department of Homeland Security

Jeremy Konyndyk
Executive Director of the COVID-19 Task Force andSenior Advisor
United States Agency for International Development(USAID)

Dr. Sarah Carter
Principal
Science Policy Consulting, LLC

Amb. (ret.) Bob Mikulak
Expert Advisor on Chemical and Biological Weapons
IssuesU.S. Department of State

Dr. Bradley Dickerson
Senior Manager, Global Chemical and Biological Security
Sandia National Laboratories

Ryan Morhard
Director, Policy and Partnerships, Concentric
Ginkgo Bioworks

Dr. Diane DiEuliis
Senior Fellow
National Defense University

Dr. Jennifer Nuzzo
Senior Scholar and Visiting Faculty, Center for Health
Security
John Hopkins Bloomberg School of Public HealthDr. James Diggans
Director, Data Science and Biosecurity
Twist Biosciences

Dr. Megan Palmer
Executive Director of Bio Policy & Leadership Initiatives,
Department of Bioengineering
Stanford University

Dr. Jessica DymondAssistant Program Area Manager, Health Protection andAssurance, National HealthJohn Hopkins Applied Physics Laboratory

Chris Park
Senior Advisor, International Security andNonproliferation
Office of the Under Secretary for Arms Control andInternational Security
U.S. Department of State

Dr. Dylan George
Vice President
Ginkgo Bioworks
Former Vice President, Technical Staff
In-Q-Tel
Dr. John Glass
Professor and Leader, JCVI Synthetic Biology Group
J. Craig Venter Institute

Carolyn Reynolds
Co-Founder
Pandemic Action Network

Amanda Glassman
Executive Vice President and Senior Fellow
Center for Global Development

Deborah Rosenblum
Executive Vice President
Nuclear Threat Initiative

Dr. William Hanage
Associate Professor of Epidemiology
Harvard T.H. Chan School of Public HealthJonas Sandbrink
Biosecurity Researcher
Future of Humanity Institute

Dr. Lawrence Kerr
Director, Office of Pandemic and Emerging Threats
Department of Health and Human Services

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Appendix B. Epidemiological Model
Summary
Developed by Dr. Ellie Graeden Trae Wallace, Talus Analytics
The epidemiological elements of the exercise scenario were developed using a standard Susceptible–
Exposed–Infectious–Recovered (SEIR) compartmentalized model. The model assumes no asymptomatic
spread. The structure of the model is summarized in Figure B-1. A lab-modified version of monkeypox
was intentionally released via aerosols in train stations in the fictional country of Brinia (population 250
million) by agents of a terrorist group operating in neighboring Arnica (population 75 million).
Through intentional modifications made by Arnican virology lab scientists sympathetic with the Arnican
terrorists, this monkeypox strain is assumed to be more contagious than naturally occurring monkeypox—
with a basic reproductive number (R0) for the modified strain of 3, as compared to 2.13 for the wildtypestrain.11 The lab-modified strain is also engineered to be resistant to the smallpox vaccine. Vaccine resistanceis assumed to be driven by the introduction of the Interleukin-4 gene, as demonstrated in previous mousepox
studies.12 We assume a case fatality rate of approximately 10 percent, which is consistent with previously
described monkeypox outbreaks.13

Modeling State Descriptions
The following bullet points summarize the states of the SEIR model and how individual model agentsprogress through them. (Additional details on each parameter are provided in Tables B-1 and B-2 on pages
30 and 31.)
• Susceptible. Initial state for all individuals in a fully predictive run. In cases where the model run
is initiated based on prior cases, the susceptible group includes the proportion of individuals notpreviously exposed.
• Exposed. Individuals move from Susceptible to Exposed when they come into contact with
infectious individuals at a rate that is determined by the number of contacts individuals have with
one another. All exposed individuals transition to mild cases (Infected1) after eight days.

11

Rebecca Grant, Liem-Binh Luong Nguyen, & Romulus Breban, “Modelling Human-to-Human Transmission of Monkeypox,” Bulletin of theWorld Health Organization 98, no. 9 (September 1 2020): 638–640, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463189/.

12

R.J. Jackson, A.J. Ramsay, C.D. Christensen, S. Beaton, D.F. Hall, & I.A. Ramshaw, “Expression of Mouse Interleukin-4 by a Recombinant
Ectromelia Virus Suppresses Cytolytic Lymphocyte Responses and Overcomes Genetic Resistance to Mousepox,” J Virol 75, no. 3 (February2001):1205–10. doi: 10.1128/JVI.75.3.1205-1210.2001. PMID: 11152493; PMCID: PMC114026.

13

WHO, “Monkeypox–Democratic Republic of the Congo,” Disease Outbreak News (October 1, 2020), https://www.who.int/emergencies/disease-outbreak-news/item/monkeypox-democratic-republic-of-the-congo.

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats• Infected1. These are mild cases. After approximately one week, 50 percent of these cases worsen,
and require hospitalization (the Infected2 state) whereas the remaining 50 percent progress to the
Recovered state.
• Infected2. These are severe, hospitalized cases, requiring non-ICU treatment. After approximately
one week, 40 percent of these cases worsen, thus requiring ICU (Infected3), whereas the remaining
60 percent progress to the Recovered state.
• Infected3. These are critical cases requiring ICU treatment. This model assumes all deaths must firstpass through this category. After approximately one week, 50 percent of these cases lead to death,
whereas the remaining 50 percent progress to Recovered.
• Recovered. This compartment includes all individuals who have already had the disease (excluding
those who died). For the purposes of the model, recovered individuals are considered to be immune
from future infection.
• Deceased. Individuals who have died as a result of the disease. All deaths result from ICU(Infected3) cases and make up approximately 10 percent of all cases.
Figure B-1. SEIR Compartmental Model Structure

γ1

Ssusceptible

β1 I1
1

E

α

I1

exposedmild infection(asymptomatic,
not infectious)(infectious)

ρ1

I2
hospitalized

ρ2

R

γ2

recovered

γ3
I3
ICU

μ
D

infectious

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

Associated parameters for each are described in Table B-1, below.
Table B-1. Key Parameters
Parameter

SymbolValue

SourceTransmission rate

Beta (β)

0.175

scenario assumption

Pre-symptomatic period–

8 days14

Mild infection duration–

14 days15

Hospital stay (recovery/death)–18 daysibid.

Asymptomatic cases

–

0%

16

Hospitalization rate

Rho1 (ρ1)

50%

ICU need for hospitalized

Rho2 (ρ2)

40%

ibid.

Death for ICU cases

Mu (μ)

50%

ibid.

–

10%

18

Total Case Fatality Rate (CFR)

17

and scenario assumption

The release in Brinia results in 150 initial infections on May 15, 2022, and 10 inadvertently infected
Arnicans. By June 1, travel from Brinia has seeded infections in the rest of the world. Elements of nationallevel response were also included in the model using a basic framework of adjusting the contact rate, Beta
(which impacts R), to represent the effects of social distancing on transmission (including lockdowns andstay-at-home orders). The global population, excluding those living in Arnica and Brinia, were divided
into three categories, reflecting the quality of public health response at the national level—designated as“Effective,” “Modest,” or “Poor.” The population of countries with “Poor” responses represent 4.4 billion
people, whereas those with “Modest” and “Effective” responses represent 1.5 billion people each. Brinia’s
response is defined as “Poor”; and Arnica’s response is defined as “Moderate.” Additionally, the fictionalcountries of Cardus and the Republic of Dranma have “Poor” and “Effective” responses respectively, andeach have populations of 60 million and 10 initial cases. The specific dates and impacts on transmission ofeach response are listed in Table B-2 page 31.
All countries react to the emerging outbreak in Brinia after Move 1 on June 5, 2022. These actions impact
the transmission rate but do not bring the total effective reproductive number of the virus below 1. All
countries act again in early 2023. For the countries with a “Poor” response, this action is still too small

14

Ellen M. Beer & V. Bhargavi Rao, “A Systematic Review of the Epidemiology of Human Monkeypox Outbreaks and Implications for
Outbreak Strategy,” PLOS Neglected Tropical Diseases (October 16, 2019), https://journals.plos.org/plosntds/article?id=10.1371/journal.
pntd.0007791.

15

Andrea M. McCollum & Inger K. Damon, “Human Monkeypox,” Clinical Infections Diseases 58, no. 2 (January 2014): 260–7, https://academic.oup.com/cid/article/58/2/260/335791.

16

Daniel B. Di Giulio & Paul B. Eckburg, “Human Monkeypox: An Emerging Zoonosis,” Lancet Infect Dis 4, no. 1 (January 2004):15–25,
https://pubmed.ncbi.nlm.nih.gov/14720564/.

17

Estimated from moderate/hospitalized and severe cases to achieve case fatality rate. Inger K. Damon, “Status of Human Monkeypox: ClinicalDisease, Epidemiology and Research,” Vaccine 29 (2011): D54-D59, https://www.sciencedirect.com/science/article/pii/S0264410X1100524X.

18

WHO, “Monkeypox,” 2019, https://www.who.int/news-room/fact-sheets/detail/monkeypox.

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

and leaves the R well above 1. The “Moderate” response countries open up in January, increasing R to
approximately 2.2, before locking down in the summer of 2023 when the outbreak is undeniable. Finally,
the “Effective” response countries lock down aggressively in February 2023 and keep R below 1 throughout
the remainder of the exercise.
The combined global pandemic leads to more than three billion cumulative cases and more than 270
million deaths by the end of December 2023. At the peak of the pandemic, nearly 500 million individuals
are infected at the same time, and there are 161 million people simultaneously in need of hospitalization.
The model was written in Python, with configuration and visualization through Jupyter notebooks.
Table B-2. Non-Pharmaceutical Intervention Dates and Impacts
Effective National Response
Date

Beta

R

6/6/220.09

1.89

2/7/230.01

0.77

Modest National Response
Date

Beta

R

6/6/220.08

1.75

1/11/23

0.11

2.17

3/11/23

0.08

1.75

7/15/23

0.007

0.728

Poor National Response

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Beta

R

6/6/220.15

2.73

1/15/23

0.085

1.82

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Strengthening Global Systems to Prevent and Respond to High-Consequence Biological Threats

About the Authors
Jaime M. Yassif, Ph.D.
Senior Fellow, Global Biological Policy and Programs, NTI
Dr. Jaime M. Yassif is Senior Fellow for Global Biological Policy and Programs at NTI, where she is leading
several major biosecurity projects focused on strengthening governance of dual-use bioscience and reducing
global catastrophic biological risks. Yassif previously served as a Program Officer at Open Philanthropy,
where she led the Biosecurity and Pandemic Preparedness initiative. In this role, she recommended andmanaged approximately $40 million in biosecurity grants, which rebuilt the field and supported workin several key areas, including developing new biosecurity programming at several leading think tanks,
establishing the Global Health Security Index, initiating new biosecurity work in China and India, andframing a new public discourse about global catastrophic biological risks. Prior to this, Yassif served asa Science and Technology Policy Advisor at the U.S. Department of Defense and worked on the Global
Health Security Agenda at the U.S. Department of Health and Human Services.
Kevin P. O’Prey, Ph.D.
Managing Partner, The Palisades Group, LLC
Dr. Kevin P. O’Prey has served as the facilitator for the annual Nuclear Threat Initiative’s Biosecurity tabletop
exercises at the Munich Security Conference. As Managing Partner at the Palisades Group, O’Prey oversees
analytical and facilitation projects for the U.S. Federal Government, private sector, and internationalorganizations. Previously, he was co-founder and president of Obsidian Analysis, Inc. and president of DFI
Government Services. He earned his Ph.D. in political science at MIT’s Security Studies Program.
Christopher R. Isaac, M.Sc.
Program Assistant, Global Biological Policy and Programs, NTI
Mr. Christopher R. Isaac is a Program Assistant for Global Biological Policy and Programs at NTI. Isaac
has been involved with synthetic biology through the Internationally Genetically Engineered Machines(iGEM) Competition since the start of his scientific career and brings with him a mixture of skills in policy,
biochemistry, and programming. Isaac holds a B.Sc. in Biological Sciences with a minor in Philosophy
and a M.Sc. in Biochemistry (Bioinformatics) from the University of Lethbridge. He is an alumnus of
the Emerging Leaders in Biosecurity Fellowship at the Johns Hopkins Center for Health Security and is amember of the iGEM Safety and Security Committee.

NTI Paper

32

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About the Nuclear Threat Initiative
NTI is a nonprofit global security organization focused on reducing nuclear and biological threats imperilinghumanity. www.nti.org

More from NTI | bio

NTI Paper
JUNE 2019

A Spreading Plague:
Lessons and Recommendations
for Responding to a Deliberate
Biological Event
SUMMARY
On the eve of the 2019 Munich Security Conference, senior leaders fromsecurity, public health, humanitarian, and political sectors participated in a
dramatic tabletop exercise designed to explore global capability to rapidly
respond to a deliberate biological event. The exercise uncovered major gaps
in coordination, information sharing, attribution, and financing. This reportpresents key findings and recommendations for urgent improvements toavoid catastrophic consequences of deliberate and other high-consequence
biological events.

Elizabeth Cameron, Ph.D., Rebecca Katz, Ph.D., M.P.H.,
Jeremy Konyndyk, M.S.F.S., and Michelle Nalabandian, M.F.S.

June 2019
A Spreading Plague: Lessons andRecommendations for Responding
to a Deliberate Biological Event
Beth Cameron, Ph.D.,
Rebecca Katz, Ph.D., M.P.H.,
Jeremy Konyndyk, M.S.F.S., andMichelle Nalabandian, M.F.S.

September 2020
Preventing Global Catastrophic
Biological Risks: Lessons andRecommendations from a Tabletop
Exercise Held at the 2020 Munich
Security Conference
Preventing Global
Catastrophic
Biological Risks

Lessons andRecommendations
from a Tabletop
Exercise Held at the2020 Munich Security
Conference

BETH CAMERON, PH.D. • JAIME YASSIF, PH.D. • JACOB JORDAN, PH.D. • JACOB ECKLES, M.P.H.

Beth Cameron, Ph.D,
Jaime Yassif, Ph.D.,
Jacob Jordan, Ph.D., andJacob Eckles, M.P.H.

For more information visit www.nti.org/bio.

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