The Biological Threat Landscape
COVID-19 killed millions. The 2004 SARS Beijing lab outbreak caused by inadequately inactivated virus killed one and exposed hundreds to quarantine. Soviet Biopreparat violated the Biological Weapons Convention at massive scale for two decades while the world remained unaware. Biological threats span natural outbreaks, accidental laboratory releases, and deliberate misuse, each requiring fundamentally different defensive strategies.
- Classify biological threats across natural, accidental, and deliberate categories
- Understand zoonotic spillover as primary mechanism for emerging infectious diseases
- Recognize historical laboratory-acquired infection incidents and their implications
- Evaluate state bioweapons programs and bioterrorism as deliberate biological threats
Introduction
Biological threats come in three flavors: natural outbreaks, accidental releases from containment failures, and deliberate misuse for harm. Each requires different defensive strategies.
Work on the natural outbreak side includes investigating COVID-19 cases, running genomic surveillance for SARS-CoV-2 variants, and supporting the Africa CDC with pathogen sequencing infrastructure. This work exists because natural spillover from animal reservoirs to humans is continuous and inevitable. Zoonotic diseases represent the majority of emerging infections threatening human populations.
But the biosecurity field must address all three threat categories. This chapter examines each systematically: their mechanisms, historical examples, current risks, and what makes them more or less likely to cause mass casualties. Understanding the threat landscape shapes appropriate defensive investments.
Natural Outbreaks: Zoonotic Spillover
The Dominance of Zoonotic Disease
Most human infectious diseases originate from pathogens circulating in non-human animals. Estimates range from 60% to 75% of human infectious diseases having zoonotic origins. This is not historical trivia. Zoonotic spillover is the primary mechanism for emerging infectious disease events in human populations.
Spillover refers to pathogen transmission from animals to humans. Factors accelerating spillover frequency include climate change, increased human mobility, wildlife trade, land-use change bringing humans into contact with animal reservoirs, and livestock production intensification. These ecological pressures create more interfaces where pathogens can cross species barriers.
COVID-19: A Recent Example
SARS-CoV-2, the virus causing COVID-19, is widely understood to have zoonotic origins. Evidence indicates a bat-borne coronavirus transmitted to humans, likely through wildlife trade or animal contact. The WHO and independent researchers concluded zoonotic origin has the “weight of available evidence” based on viral genomics and epidemiological investigation.
The scientific consensus supports natural zoonotic spillover, consistent with the precedent of SARS-CoV-1 and MERS-CoV. Laboratory origin hypotheses have been raised but lack direct supporting evidence. The precise intermediate host and geographic origin remain subjects of ongoing research. The debate illustrates how outbreak origins can become politically charged, complicating objective investigation. What is clear: the pandemic underscored the critical need for understanding human-animal interfaces to prevent future outbreaks.
The COVID-19 pandemic killed millions globally, disrupted economies, overwhelmed healthcare systems, and demonstrated gaps in international preparedness that the 2019 Global Health Security Index predicted.
Ebola: Fruit Bat Reservoir
Ebola Virus Disease (EVD) is a severe hemorrhagic fever with zoonotic origin. The natural reservoir is believed to be fruit bats from the Pteropodidae family. Non-human primates can transmit Ebola to humans but are incidental hosts (they develop severe, often fatal illness rather than serving as reservoir species).
Ebola spillover events have increased in frequency since 1994, primarily occurring in tropical rainforest regions of Central and West Africa. Research suggests spillover intensity can be seasonal and influenced by vegetative cover and human population density. Each outbreak requires rapid containment to prevent transmission chains in human populations.
The 2014-2016 West Africa Ebola outbreak killed over 11,000 people and exposed weaknesses in WHO’s emergency response capacity, leading to establishment of the World Health Emergencies program.
Pandemic Influenza: Avian and Swine Origins
Influenza pandemics throughout history originated from zoonotic influenza A viruses, primarily from avian (bird) and swine (pig) reservoirs. For a zoonotic influenza virus to cause a pandemic, it must infect humans AND gain capacity for efficient human-to-human transmission through mutation or genetic reassortment.
Pigs serve as “mixing vessels” where different influenza viruses can recombine to produce novel pandemic strains. Examples include avian influenza A viruses (H5N1, H7N9) and the 2009 H1N1 pandemic strain of swine origin.
The WHO continuously monitors influenza evolution and coordinates global vaccine development and distribution responses to pandemic threats.
Accidental Releases: Laboratory-Acquired Infections
Lab-Acquired Infections as Occupational Hazard
Laboratory-acquired infections (LAIs) are infections contracted in laboratory environments, typically medical research facilities or hospitals. These are occupational hazards for laboratory workers. LAIs result from exposure to bacteria, viruses, fungi, or parasites through multiple routes: inhalation of aerosols, percutaneous inoculation (needle sticks, cuts, animal bites), direct mucous membrane contact, or ingestion.
Common bacterial causes include Brucella species, Shigella species, Salmonella species, Mycobacterium tuberculosis, and Neisseria meningitidis. Viral agents include Hepatitis B, Hepatitis C, and HIV in diagnostic laboratories.
Critical problem: LAIs are widely believed to be underreported due to concerns about professional reprisal and stigma. This underreporting prevents accurate risk assessment and improvement of safety protocols.
Prevention relies on robust biosafety programs including risk assessment, strict containment measures, adherence to safe work practices, comprehensive training, and accessible employee health programs. Human error is a significant contributing factor to LAI incidents.
The 1977 H1N1 “Russian Flu”: Frozen Strain Release
In 1977, an H1N1 influenza strain reappeared after a 20-year absence, causing a pandemic that primarily affected people under 25 years old. Genetic analysis revealed the virus was nearly identical to strains circulating in the 1950s, missing decades of expected evolutionary change.
Evidence for lab origin: The strain’s genetic sequence was “frozen in time,” matching 1950 isolates far too closely for natural evolution. Multiple lines of evidence point to release from a laboratory freezer:
- Many 1977 isolates were temperature-sensitive, a phenotype typical of live attenuated vaccine development
- Outbreaks appeared nearly simultaneously in three locations in northeastern China, inconsistent with natural spread
- The 1976 U.S. “swine flu” scare had triggered renewed interest in H1N1 vaccine research using stored 1950s strains
Most likely scenario: Researchers in the USSR or China used frozen 1950s H1N1 for vaccine trials during the 1976 swine flu scare, and an incompletely attenuated strain escaped during challenge experiments. Virologist Peter Palese reported this conclusion based on personal communication with researchers involved.
Consequences: The outbreak caused relatively mild illness because older adults had immunity from pre-1957 exposure. The virus became endemic and continued circulating until 2009. This incident is now cited in gain-of-function research debates as a cautionary example of pandemic-potential pathogens escaping from research settings.
The 1978 Birmingham Smallpox Outbreak
In September 1978, Janet Parker became the last person recorded to die from smallpox. She was a medical photographer at the University of Birmingham Medical School who worked in a darkroom above the laboratory where smallpox research was conducted.
Timeline: Parker developed symptoms on August 11, 1978, initially misdiagnosed as chickenpox. On August 20, she was hospitalized with confirmed Variola major. After a month-long battle with the disease, she died on September 11, 1978.
Transmission cascade: Parker’s mother contracted smallpox but survived. Her father died of a heart attack during a hospital visit. Nearly 500 people who had contact with Parker were quarantined.
Investigation: The Shooter Inquiry concluded the virus likely traveled through service ducts from the smallpox laboratory below Parker’s darkroom. The exact transmission route remains debated, but the source was clearly the Medical School laboratory.
Human cost beyond the disease: Henry Bedson, the laboratory director, was devastated by his role in the outbreak. On September 1, 1978, before Parker’s death, he died by suicide.
Legacy: This incident directly led to consolidation of all known smallpox stocks to two WHO-authorized repositories: CDC in the United States and the Vector Institute in Russia. It demonstrated that even “controlled” research on eradicated pathogens carries risks that can prove fatal.
The 2004 SARS Beijing Laboratory Outbreak
In April 2004, a SARS outbreak in China traced back to a laboratory in Beijing. Two researchers (a 26-year-old female postgraduate student and a 31-year-old male postdoc) working at the Chinese Institute of Virology (part of China’s CDC) were infected in separate incidents.
Root cause: Inadequately inactivated SARS virus transferred from a high-containment area to a different laboratory with lower biosafety levels.
Transmission cascade: The female student infected her mother (who died) and a nurse. The nurse infected five additional individuals, creating “third-generation” infections. The laboratory outbreak produced 9 confirmed cases and 1 death, requiring quarantine of hundreds to prevent further spread.
WHO assessment: Critical biosafety breaches and failures to follow safety guidelines.
Significance: This was one of several laboratory-related SARS outbreaks occurring AFTER the main 2003 epidemic was controlled. It demonstrated that high-consequence pathogens remain dangerous in research settings even when outbreak threats have passed.
The 2014 CDC Smallpox Discovery
In July 2014, NIH workers discovered vials labeled “variola” (smallpox virus) in an unsecured storage area at an FDA laboratory in Bethesda, Maryland. The vials appeared to date from the 1950s.
Why this mattered: Smallpox was globally eradicated in 1980. Under international agreement, known smallpox samples are permitted only in two secure repositories: CDC in Atlanta and Vector Institute in Russia. This laboratory was NOT authorized to possess smallpox.
Investigation: Vials were transferred to CDC’s high-containment facility. PCR testing confirmed variola virus DNA. Further analysis established all six vials contained live, viable smallpox virus. No evidence of vial breaches or exposure was identified.
Context: This incident occurred alongside other CDC mishandlings of dangerous pathogens (anthrax, Ebola) in 2014, raising concerns about biosafety practices in federal laboratories.
Key lesson: Even after decades, forgotten biological materials can pose risks. Inventory control and laboratory security remain critical.
Deliberate Misuse: Bioterrorism and State Programs
Bioterrorism: Intentional Biological Attacks
Bioterrorism involves intentional release or dissemination of biological agents (bacteria, viruses, fungi, toxins) to cause illness or death in people, animals, or plants, often for political or social objectives. Risk of bioterrorist attacks is believed to be increasing.
Biological agents appeal to malicious actors because they can be difficult to detect, may not cause illness for hours to days (allowing perpetrator escape), and some agents (smallpox) spread person-to-person while others (anthrax) do not.
CDC Category A agents (highest priority bioterrorism threats due to high mortality, easy transmissibility, potential for public panic):
- Anthrax (Bacillus anthracis)
- Botulism (botulinum toxins)
- Plague (Yersinia pestis)
- Smallpox (variola virus)
- Tularemia (Francisella tularensis)
- Viral hemorrhagic fevers (Ebola, Marburg, Lassa, others)
Category B agents are moderately transmissible with lower mortality. Category C agents are emerging pathogens that could be engineered for mass dissemination.
Historical Bioterrorism Events
Ancient and Medieval Use: Historical accounts describe catapulting plague-infected corpses into besieged cities (e.g., Caffa in 1346) and poisoning water sources with cadavers. Effectiveness is debated by historians but demonstrates long-standing awareness of biological weapons potential.
World War I: Germany reportedly attempted covert operations using anthrax and glanders to infect animals and contaminate animal feed in enemy countries.
Japan’s Unit 731 (WWII): Conducted extensive offensive biological warfare research and attacks in China, deliberately releasing plague, cholera, and typhoid. Caused tens of thousands of deaths. Represented state-level biological warfare program with large-scale research infrastructure.
Rajneeshee 1984: Cult members contaminated salad bars in Oregon with Salmonella, causing 751 illnesses. Demonstrated feasibility of foodborne biological attack by non-state actor.
Aum Shinrikyo 1993: Despite significant resources, dedicated personnel, and scientific expertise, Aum Shinrikyo’s biological weapons attempts all failed. Their 1995 sarin chemical attack on Tokyo subway succeeded (12 deaths, 5,000 injuries), highlighting practical difficulty of effective biological weapons deployment compared to chemical weapons.
2001 Amerithrax: Letters containing Bacillus anthracis spores (Ames strain) mailed to news media and U.S. Senators. Five deaths, 22 infections. Investigation implicated Dr. Bruce Ivins, a scientist at U.S. government biodefense lab. Demonstrated insider threat with legitimate access to select agents. Led to major U.S. biosecurity policy reforms.
State Bioweapons Programs
State bioweapons programs involve government development and potential use of biological agents as biological warfare component.
United States (1943-1969): Offensive biological weapons program developed and stockpiled anthrax, tularemia, botulinum toxin, and other agents. Unilaterally ended in 1969, shifting to biodefense-only focus.
Soviet Union/Biopreparat (1973-1992): Despite signing the BWC, operated the world’s largest offensive biological weapons program. Weaponized Marburg hemorrhagic fever, tularemia, anthrax, smallpox, plague. Revealed through defector testimony (Vladimir Pasechnik 1989, Ken Alibek 1992). Demonstrated that BWC without verification can be violated at massive scale for decades.
Current Concerns: Countries alleged to possess or have pursued biological weapons capabilities include North Korea, Iran, and others. Verification remains challenging due to dual-use nature of legitimate biological research.
Threat Assessment Frameworks
Systematic evaluation of biological threat likelihood and potential impact involves:
Agent Characteristics: Weaponization potential based on ease of production, stability, transmissibility, infectivity, mortality rates, incubation period, availability of countermeasures and detection methods.
Perpetrator Capabilities: Resources, expertise, motivations of potential adversaries (state actors, terrorist groups, individuals). Access to materials, equipment, technical knowledge.
Vulnerability Assessment: Potential targets (population centers, livestock, crops, water supplies) and defensive weaknesses.
Attack Scenarios: Dissemination methods (aerosols, food/water contamination, direct exposure) and scale.
Consequence Assessment: Public health, economic, social impacts. Response and recovery capacity.
Organizations like CDC, NIAID, and Department of Homeland Security conduct risk assessments to prioritize biodefense efforts. International cooperation through the Biological Weapons Convention remains crucial for prevention.
Comparing Threat Categories
Likelihood vs. Consequence
Natural Outbreaks:
- Likelihood: High (continuous zoonotic spillover)
- Consequence: Variable (COVID-19 killed millions; most spillovers fizzle)
- Inevitability: Climate change and ecological disruption increasing interface
Accidental Releases:
- Likelihood: Moderate (thousands of labs worldwide handling dangerous pathogens)
- Consequence: Usually contained but can spark outbreaks (2004 SARS Beijing)
- Preventability: High (robust biosafety reduces risk dramatically)
Deliberate Misuse:
- Likelihood: Low (significant barriers despite fears)
- Consequence: Potentially catastrophic (depends on agent and delivery)
- Trend: Dual-use research and synthetic biology lowering knowledge barriers
Barriers to Biological Weapons Development
Historical evidence (Aum Shinrikyo failures, limited bioterrorism successes) suggests significant barriers:
Technical Challenges:
- Culturing and weaponizing pathogens requires expertise
- Aerosol delivery is difficult to execute effectively
- Environmental stability varies by agent
- Protective equipment and vaccine availability for some agents
Material Access:
- Select agent regulations restrict pathogen access
- DNA synthesis screening (though imperfect)
- Laboratory security measures
Tacit Knowledge:
- Hands-on laboratory experience difficult to acquire outside legitimate research settings
- Troubleshooting fermentation, formulation, delivery requires practical training
However, these barriers are not absolute. Synthetic biology, gene editing tools (CRISPR), and potentially AI-assisted design are lowering knowledge barriers over time. This drives biosecurity concern about future threat landscape.
This chapter is part of The Biosecurity Handbook.