Professional Documents
Culture Documents
A Guide To Investigating Outbreak Origins: Nature Versus The Laboratory
A Guide To Investigating Outbreak Origins: Nature Versus The Laboratory
www.nonproliferation.org www.middlebury.edu/institute
The authors would like to thank Dr. Milton Leitenberg, Dr. John Hart, Ambassador
Bob Mikulak, and Dr. Danielle Lohman for their detailed reviews of this article, the
recommendations of which have vastly improved the final product, even when con-
sensus feedback was not unanimous. In addition, the authors would like to thank
Rhianna Tyson Kreger, Anne Marie Steiger, and David Steiger for their editing and
production of the paper. This paper is dedicated to, and in honor of, all who have
sacrificed to protect our global community during the COVID-19 pandemic and
others yet to come.
The views, judgments, and conclusions in this report are the sole representations of the
authors and do not necessarily represent either the official position or policy or bear the
endorsement CNS or the Middlebury Institute of International Studiehs at Monterey.
Richard Pilch
Miles Pomper
Jill Luster
Filipa Lentzos
Contents
Introduction .................................................................................................................................................... 1
Background .................................................................................................................................................... 2
Conclusion ...................................................................................................................................................... 24
3
https://apps.who.int/gb/ebwha/pdf_files/WHA73/A73_R1-en.pdf, pg. 6, item 9(6).
4
https://geneva.usmission.gov/2020/05/19/explanation-of-position-covid-19-re-
sponse-resolution/
5
See, for example, https://www.forbes.com/sites/jackbrewster/2020/05/10/a-time-
line-of-the-covid-19-wuhan-lab-origin-theory/#638e124a5aba; https://www.nytimes.
com/2020/05/03/us/politics/coronavirus-pompeo-wuhan-china-lab.html; https://foreign-
policy.com/2020/05/01/coronavirus-trump-pandemic-pompeo-attack-china/
6
Only a few months before COVID-19, a different laboratory – and outbreak – dominated
American headlines, when the US House of Representatives launched a formal investiga-
tion into renewed allegations that the 1975 emergence of Lyme disease in Lyme, Con-
necticut may have been linked to the nearby Plum Island Animal Disease Center (PIADC)
(https://chrissmith.house.gov/uploadedfiles/final_lyme_ig_amendment.pdf). Despite the
questionable veracity of these allegations, the supporting evidence aligns with that of the
SARS-CoV-2 laboratory origin hypothesis: (1) Laboratories around the world have accidents,
including in the United States; (2) One laboratory in close proximity to the initially identified
cases, PIADC, had come under scrutiny for reported safety lapses; (3) That same labora-
tory was responsible for studying unknown, potentially zoonotic disease agents in animal
populations; and (4) If the causative agent of Lyme disease (Borrelia burgdorferi) was being
studied there, and an accident happened, it could plausibly have been introduced into the
neighboring human population by any number of well-documented routes of laboratory “es-
cape,” including on/in a laboratory worker traveling on one of only two ferries serving PIADC,
birds migrating along the north-south Atlantic Flyway, or wildlife known to move between the
island and mainland (See, for example, https://www.gao.gov/assets/130/120213.html;
https://www.nytimes.com/2004/08/22/nyregion/plum-island-reports-disease-outbreak.
html). Against the laboratory origin hypothesis, again like SARS-Co-V: there is a well-docu-
mented mechanism for animal to human spillover of biological agents like B. burgdorferi,
including in the area where Lyme disease was initially detected (babesiosis, for example;
see Diuk-Wasser MA, Liu Y, Steeves TK, et al. Monitoring human babesiosis emergence
through vector surveillance New England, USA. Emerg Infect Dis. 2014; 20(2):225-231.
doi: 10.3201/eid2002.130644), and the ensuing spread follows expected epidemiological
characteristics of a natural event. The bottom line: as with SARS-CoV-2, regardless of Lyme
disease’s origin, the risk of both high-consequence laboratory mishaps and spillover at the an-
imal-human interface is real, and the disease is now affecting populations around the world.
7
The need for a credible investigative approach to COVID-19’s origin and what that
might entail was described by Dr. Filippa Lentzos in a pair of May 2020 articles in the
Bulletin of the Atomic Scientists, both of which informed our proposed methodology.
Dr. Lentzos’s articles are available at: https://thebulletin.org/2020/05/natural-spill-
over-or-research-lab-leak-why-a-credible-investigation-in-needed-to-determine-the-ori-
gin-of-the-coronavirus-pandemic/; https://thebulletin.org/2020/05/will-the-who-call-for-an-in-
ternational-investigation-into-the-coronaviruss-origins/
2. Analytical Epidemiology
Why/How Laboratory Risk
a. Assess the epidemiological triangle Confirmed?
b. Assess the genome No
Yes
Natural Laboratory
Original Origin
Confirmed? Confirmed?
No No
Yes Yes
2 April
10pm
4am, 1pm
4pm, 10am
1am 7pm
zone. An April 2 exposure date aligned with the expected range of time
to presentation of symptoms (i.e., incubation period) and clinical course
observed in reported cases. A 1999 insider account of the incident
identified Compound 19 as a biological-weapons-production facility and
cited a laboratory mishap involving the removal of an exhaust filter and
subsequent aerosol release of anthrax spores, which were carried by
the wind along the exposure zone, as the cause of the outbreak.9
12
Zhou, P., Yang, X., Wang, X. et al. A pneumonia outbreak associated with a new coronavirus of
probable bat origin. Nature 579, 270–273 (2020). https://doi.org/10.1038/s41586-020-2012-7
13
While the role of the polybasic cleavage site has yet to be confirmed, the polybasic cleavage
site differs from typical monobasic cleavage sites in that it offers multiple (“poly,” as opposed
to “mono,” meaning one) nucleic acids where the viral binding protein, called the spike or “S”
protein, can be cut and thus activated to enable infection of human cells.
14
Zhen, Deverman, and Chan. SARS-CoV-2 is well adapted for humans. What does this mean
for re-emergence? bioRxiv, 2 May 2020. doi: https://doi.org/10.1101/2020.05.01.073262.
15
See, for example, Pascall DJ, Nomikou K, Bréard E, Zientara S, Filipe AdS, Hoffmann B, et al.
(2020) “Frozen evolution” of an RNA virus suggests accidental release as a potential cause of arbo-
Collected samples were sent to the local Institute for Animal Health
for analysis, which identified the infecting agent as FMD virus strain
O1BFS 1860. The strain was strikingly similar to a 1967 reference
strain used at the same Pirbright laboratory for vaccine production.16
Because the strain lacked the years of amassed mutations that would
be expected in a naturally occurring outbreak, a laboratory origin was
virus re-emergence. PLoS Biol 18(4): e3000673. https://doi.org/10.1371/journal.pbio.3000673.
16
Because three different laboratories at Pirbright worked with the strain, the sequence of
each differed very slightly due to ongoing mutations.
20
Pilch R and Pomper M. A Guide to Getting Serious about Bio-Lab Safety. War on the Rocks. June
1, 2020. https://warontherocks.com/2020/06/a-guide-to-getting-serious-about-bio-lab-safety/
21
Note the possibility of deliberate omissions or inaccuracies.
22
PubMed consolidates the vast majority of scientific references into a single, searchable
database (https://pubmed.ncbi.nlm.nih.gov/), while databases of the National Center for
Biotechnology Information (https://www.ncbi.nlm.nih.gov/) contain up-to-date information on
all deposited genetic sequences, genome assemblies, and protein sequences and structures.
The search process may begin with a scientist’s name, for example from the laboratory’s di-
rectory if one is available in the open source, or with the laboratory name as the search term,
from which scientist names and research areas may be derived.
23
See, for example, the National Institutes of Health’s Project Reporter; a representative
grant report of coronavirus funding related to the Wuhan Institute of Virology: https://bit.
ly/35w8yq2
Diagnostic laboratories
Research laboratories
27
See, for example, National Research Council. 2004. Biotechnology Research in an Age of
Terrorism. Washington, DC: The National Academies Press. https://doi.org/10.17226/10827.
(“Fink Report”)
32
For example, the US Federal Select Agent Program, which controls the possession, use,
and transfer of dangerous biological agents (and toxins) deemed by the US government
as holding the potential to pose a severe threat to public, animal, or plant health, releases
an annual safety report of laboratories under its purview; the 2018 report documented
193 accidents the majority of which were the result of conducting work without appropri-
ate safety equipment. See: https://www.selectagents.gov/resources/FSAP_Annual_Re-
port_2018_508.pdf.
33
For example, laboratories accredited to the International Organization for Standardization’s
(ISO) “General Requirements for the Competence of Testing and Calibration Laboratories”
standard (ISO/IEC 17025:2017) are required to maintain a range of records spanning training,
maintenance, and other relevant activities. See: https://www.iso.org/standard/66912.html
34
See for example, (a) reports on laboratory safety in Wuhan: Josh Rogin, “State Department
cables warned of safety issues at Wuhan lab studying bat coronaviruses,” Washington Post,
April 14, 2020; John Xie, “Chinese Lab with Checkered Safety Record Draws Scrutiny over
Covid-19,” VOA News, April 21, 2020, https://www.voanews.com/covid-19-pandemic/chi-
nese-lab-checkered-safety-record-draws-scrutiny-over-covid-19; and (b) reports on accidental
releases of SARS from a related Beijing laboratory: Robert Walgate, “SARS escaped Beijing
lab twice: Laboratory safety at the Chinese Institute of Virology under close scrutiny,” The
Scientist, April 24, 2004, https://www.the-scientist.com/news-analysis/sars-escaped-bei-
jing-lab-twice-50137. Rosie McCall, “Almost 100 Lab Workers in China Infected With Po-
tentially Deadly Pathogen,” Newsweek, December 17, 2019, https://www.newsweek.com/
almost-100-lab-workers-china-infected-potentially-deadly-pathogen-1477652.
35
See, for example, https://thebulletin.org/2019/02/human-error-in-high-biocontainment-
labs-a-likely-pandemic-threat/
Differentiating Deliberate
Outbreaks
As with outbreaks of natural and laboratory origin, the global
community must be able to differentiate between intentional and
unintentional outbreaks in order to optimally identify, manage,
and attribute deliberate events. Such investigation differs from
distinguishing between outbreaks of natural and laboratory origin in
two important ways: (1) law enforcement must become involved either
at the national level, possibly with support from other states, or at
the international level under the UN Secretary-General’s Mechanism,
likely in coordination with other relevant international organizations
such as the WHO or World Organization for Animal Health; and
(2) chain-of-custody must be maintained to ensure the integrity of
evidence, requiring careful documentation and quality control of
sample collection, transport, and analysis.
In the second and arguably more likely instance, ill human and/
or animal populations would be expected to trigger an outbreak
investigation following the initial steps of the methodology described
in this article, namely: (1) descriptive epidemiology to determine
the who, what, when, and where of the outbreak; and (2) analytical
epidemiology, including an assessment of the epidemiological
triangle and infecting agent genome, to determine the why and how
of the outbreak. Findings at each step may suggest the possibility of
a deliberate origin (Figure 6), prompting immediate assessment of
potential nefarious sources.
Miles Pomper
Miles Pomper is a senior fellow in the Washington, DC, office of
CNS. His work focuses on nuclear energy, nuclear nonproliferation,
nuclear security, and nuclear-arms control. He holds a Master’s
degree in international affairs from Columbia University and a
Master’s degree in journalism from Northwestern University.
Jill Luster
As a senior research associate for CNS, Jill Luster supports multiple
projects related to nonproliferation, machine learning, One Health
security, and biological security and safety.
Filippa Lentzos
Filippa Lentzos, PhD, is a senior research fellow at King’s College
London, where she has a joint appointment in the Department of
War Studies and the Department of Global Health & Social Medicine.
She is also: an associate senior researcher with the armament and
disarmament program at the Stockholm International Peace Research
Institute (SIPRI); a biosecurity columnist at the Bulletin of the Atomic
Scientists; an editor of the social science journal BioSocieties; and
the nongovernmental organizations coordinator for the Biological and
Toxin Weapons Convention. A biologist and social scientist by training,
Dr. Lentzos has researched and been actively involved in biological
disarmament and nonproliferation for over 15 years. Her 450-page
edited volume Biological Threats in the 21st Century: The politics,
people, science and historical roots was published by Imperial College
Press in 2016. For more about her work, see www.filippalentzos.com
and for regular updates follow her on Twitter: @FilippaLentzos.
#46 • Options for a Verifiable Freeze on #30 • Crowdsourcing Systems #13 • Trafficking Networks for Chemical
North Korea’s Missile Programs and Potential Applications in Weapons Precursors: Lessons from the
Nonproliferation 1980s Iran-Iraq War
#45 • The Finger on the Button
#29 • The Verification Clearinghouse: #12 • New Challenges in Missile
#44 • Eyes on U: Opportunities, Debunking Websites and the Potential Proliferation, Missile Defense, and Space
Challenges, and Limits of Remote for Public Nonproliferation Monitoring Security
Sensing for Monitoring Uranium Mining
and Milling #28 • Geo4nonpro.org: A Geospatial #11 • Commercial Radioactive Sources:
Crowdsourcing Platform for WMD Surveying the Security Risks
#43 • North Korea’s International Verification
Scientific Collaborations: Their Scope, #10 • Future Security in Space:
Scale, and Potential Dual-Use and #27 • Searching for Illicit Dual Use Commercial, Military, and Arms Control
Military Significance Items in Online Marketplaces: A Semi- Trade-Offs
Automated Approach
#42 • The Other Fissile Material: #09 • The 1971 Smallpox Epidemic
Strengthening National and #26 • 2016 Symposium Findings in Aralsk, Kazakhstan, and the Soviet
International Plutonium Management on Export Control of Emerging Biological Warfare Program
Approaches Biotechnologies
#08 • After 9/11: Preventing Mass
#41 • Monitoring Uranium Mining and #25 • Outlawing State-Sponsored Nuclear Destruction Terrorism and Weapons
Milling in India and Pakistan through Procurement Programs and Recovery of Proliferation
Remote Sensing Imagery Misappropriated Nuclear Goods
#07 • Missile Proliferation and Defences:
#40 • Monitoring Uranium Mining #24 • Strengthening the ROK-US Nuclear Problems and Prospects
and Milling in China and North Korea Partnership
through Remote Sensing Imagery #06 • WMD Threats 2001: Critical Choices
#23 • Replacing High-Risk Radiological for the Bush Administration
#39 • Safeguards and Verification in Materials
Inaccessible Territories #05 • International Perspectives on
#22 • A Blueprint to a Middle East WMD- Ballistic Missile Proliferation and
#38 • Geo4Nonpro 2.0 Free Zone Defenses
#37 • All the World Is Staged: An Analysis #21 • Biotechnology E-commerce: A #04 • Proliferation Challenges and
of Social Media Influence Operations Disruptive Challenge to Biological Nonproliferation Opportunities for New
against US Counterproliferation Efforts in Arms Control Administrations
Syria
#20 • Countering Nuclear Commodity #03 • Nonproliferation Regimes at Risk
#36 • North Korea’s Information Smuggling: A System of Systems
Technology Networks #02 • A History of Ballistic Missile
#19 • Alternatives to High-Risk Development in the DPRK
#35 • Countering North Korean Radiological Sources
Procurement Networks Through #01 • Former Soviet Biological Weapons
Financial Measures: The Role of #18 • Stories of the Soviet Anti-Plague Facilities in Kazakhstan: Past, Present,
Southeast Asia System and Future