Since the COVID-19 pandemic began six years ago, controversy has raged over its origin. As recently as April 2025, the White House officially stated on its website that the virus originated in a laboratory in Wuhan, China. Another hypothesis is that the virus was deliberately engineered by the Chinese government or military as a biological weapon, though this scenario has been deemed dubious. Despite these claims, the most widely supported theory is the “natural spillover” hypothesis, in which the virus was transmitted to humans from animal sources, including wildlife markets in Wuhan.¹

But the “lab leak” hypothesis has remained plausible, and some circumstantial evidence supports it.  Such events have historical precedents. 

In general, standard microbiology laboratories can pose infectious disease risks to personnel through unintended exposures. Numerous published reports document laboratory-associated cases of bacterial infections, including typhoid, cholera, glanders, brucellosis, tularemia, and tetanus. In addition, several viral infections have been reported, including arboviruses, hepatitis, and Venezuelan equine encephalitis. Despite this documented experience, such laboratories working with infectious agents have not been shown to pose a threat to the community.²

In contrast, when infectious agents accidentally escape containment from specialized research laboratories, they can trigger community outbreaks and pose significant risks to the public. At least 70 such incidents have occurred over the past 75 years. These include the 1977 re-emergence of the H1N1 influenza virus in China and the Soviet Union; the 1995 epidemics of Venezuelan equine encephalitis in Venezuela and Colombia; the 2007 foot-and-mouth disease virus outbreak in England; and the 2019 brucella leak in China. These outbreaks were typically marked by unusual strain characteristics, atypical clinical manifestations or altered demographics, unusual geographic features or epidemiological patterns, and delayed government action and public communication.³  

While the original COVID epidemics in the early 2000s, involving SARS-CoV-1 in Singapore, Taiwan, and China, and MERS-CoV in Saudi Arabia, were not caused by a laboratory leak, a few isolated, small-scale laboratory accidents were reported to have occurred with these agents in 2004, affecting only researchers studying the virus.⁴

In some cases, laboratories researching infectious agents as bioweapons or for biodefense have accidentally released dangerous pathogens.

There have been at least two significant episodes in recent years involving accidental laboratory releases of serious infectious pathogens from military facilities studying them for weaponization. The most infamous accident occurred in 1979 at a secret military facility in the Soviet city of Sverdlovsk (now Yekaterinburg), Russia. An unreplaced exhaust air filter allowed aerosolized Bacillus anthracis spores to escape, resulting in at least 66 regional deaths from anthrax. Numerous livestock were also affected. For years, local authorities blamed “contaminated meat,” but the truth emerged much later.⁵

Another incident occurred in 1971 in Aralsk, Kazakhstan.  Here, an accidental release of a weaponized aerosolized smallpox strain infected 10 people and killed 3, including those who had previously been vaccinated.⁶

Over the past 40 years, numerous other high-risk, human-caused pathogen exposure events have been recorded. These have occurred in research laboratories throughout the United States, Russia, Japan, Iraq, North Korea, and elsewhere. While many of these laboratories conducted basic science research, some operated programs intended to develop bioweapons or investigate biodefense strategies. Agents under study included smallpox, anthrax, cholera, brucella, Q fever, and various viruses, including West Nile, Ebola, and dengue. In some cases, the spread of infection led to clinical illness, hospitalization, or even death.⁷

Because of safety risks, microbiology laboratories are categorized into four containment levels, designated BSL-1 through BSL-4. BSL-3 laboratories focus on agents that cause serious or lethal respiratory diseases and require safety equipment such as controlled directional airflow, double-door entry, and high-quality air filters. BSL-4 laboratories handle high-consequence, life-threatening exotic pathogens with no available treatments or vaccines (such as Ebola) and require workers to wear full-body, air-supplied, positive-pressure suits and to use dedicated decontamination showers upon exiting the facility.⁸

Using microorganisms or infected samples to cause public terror and panic has been a bioterrorism and warfare tactic for centuries. In modern times, examples include the infamous “Unit 731,” a Japanese epidemic research laboratory established in 1932, which was dedicated in part to investigating germ warfare strategies. Human subjects were inoculated with various organisms, including cholera, smallpox, botulism, anthrax, and various venereal diseases, and then left untreated to study the diseases' effects. The Nazis conducted research on the effects of various vaccines and drugs on prisoners infected with Rickettsia prowazekii or hepatitis A virus, although they apparently never used biological weapons during World War II. Nevertheless, because of the fear that the Germans might attack with biological weapons, in 1942 the United States War Research Service was created and operated a biological defense research laboratory at Fort Detrick, Maryland, as well as other facilities elsewhere. The Soviet Union also operated its own biological weapons program.⁹

In recent years, biological weapons have been used by non-state actors. In 1984, the Rajneesh cult, a religious movement, intentionally contaminated salad bars at several Oregon restaurants with Salmonella typhimurium, resulting in 751 cases, 45 of whom required hospitalization. Shortly after the September 11, 2001, World Trade Center attack, several of the country’s political leaders received mail containing anthrax spores. Of the 22 people who became infected, 5 died. Although authorities traced the bacillus strain to the U.S. Army’s laboratory at Fort Detrick, they never identified the perpetrator(s) ⁹

The recent intensification of military action in the Middle East has raised concerns among Western intelligence agencies that Iran may be pursuing an offensive biological weapons capability. Despite Iran’s ratification of the Biological Weapons Convention in 1973, the program is believed to have accelerated in the late 1980s, spurred by the unconventional attacks Iran endured during the Iran-Iraq War. Importantly, Iran has shifted its biological weapons research away from dedicated military sites and embedded it within civilian institutions, such as the Pasteur Institute of Iran, in Tehran. While the deliberate use of biological weapons by Iran is said to remain unlikely, the risk of accidental pathogen release is real.^10,11

Recent advances in genetic engineering allow alterations to an organism's DNA, enabling it to produce desired new traits.  This raises the possibility that biological weapons could be reprogrammed to enhance infectiousness or resistance to antibiotics.¹²

This discussion sets the context for Annie Jacobsen’s new book, Biological War: A Scenario. In a largely fictionalized tale, a genetically modified version of the plague bacterium, Yersinia pestis, is accidentally released from a BSL-4 laboratory in Koltsovo, Russia. Despite the laboratory’s remote location in Siberia, this highly virulent agent spreads rapidly worldwide, initially carried by a single individual and soon disseminated exponentially through direct contagion. This leads to a global pandemic that ultimately results in an existential human catastrophe.

I won't reveal more plot details, but I urge readers to experience the power of the author’s prose firsthand. Jacobsen’s narrative is gripping. The frightening scenario she constructs is grounded in fact, naming real people and places and linking them to real historical events. Interviews with 52 individuals in reputable positions in government, scientific research, and epidemiologic scholarship strengthen the scenario’s plausibility.

Copious notes, an extensive bibliography, and a detailed index further support the credibility of what Jacobsen describes. The publisher, Random House, issued this work in a “large print edition,” making it easy and entertaining to read and digest, despite its substantial content.

 Moreover, documented historical events and the plausibility that COVID-19 may have originated via a “lab leak” should help the reader appreciate that the risk of accidentally releasing potentially devastating microorganisms is real.

REFERENCES

1. Yoo, JH. On the Controversies Surrounding the Lab-leak Theory of COVID-19. J Korean Med Sci. 2025 Apr 22;40(16):e153. doi: 10.3346/jkms.2025.40.e153.

2. National Research Council (US) Committee on Hazardous Biological Substances in the Laboratory. Biosafety in Microbiological and Biomedical Laboratories. National Academies Press (US); 1989. 

3. Dhawan, S, et al. Epidemiological Indicators of Accidental Laboratory-Origin Outbreaks. Epidemiol Infect 2026 Jan 2;154:e16. doi: 10.1017/S0950268825100915.

4. de Wit, E, et al. SARS and MERS: Recent Insights into Emerging Coronaviruses. Nat Rev Microbiol.2016 Jun 27;14(8):523-34. doi: 10.1038/nrmicro.2016.81.

5. Meselson, M, et al. The Sverdlovsk Anthrax Outbreak of 1979. Science 1994 Nov 18;266(5188):1202-8. doi: 10.1126/science.7973702.

6. Tucker, JB and Zilinskas, RA. The 1971 Smallpox Epidemic in Aralsk, Kazakhstan and the Soviet Biological Warfare Program. Chemical and Biological Weapons Nonproliferation Project. Monterey Institute of International Studies, 2002. http://cns.miis.edu.

7. Manheim, D and Lewis, G. National Institutes of Health. High-risk Human-caused Pathogen Exposure Events from 1975-2016, 26 September 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC9274012/.

8. National Institutes of Health. Biosafety Level (BSL) Laboratories.26 September 2026. www.niaid.nih.gov/research/biosafety-labs.

9. Barras, V and Greub, G, History of Biological Warfare and Bioterrorism. Clin Microbiol Infect. 2014 Jun;20(6): 497-502. doi: 10.1111/1469-0691.12706.

10. Nelson, C. The Threat No One is Talking About in Iran. Royal United Services Institute (RUSI). 23 March 2026. https://www.rusi.org.

11. Jha, AK. The US Needs to be Worried About Iranian Biological Materials. First Opinion. 25 March 2026. https://www.statnews.com/2026/03/25/iran-biological-materials-bioweapon-surveillance/.

12. National Institutes of Health. National Human Genome Research Institute. 26 September 2026. https://www.genome.gov/genetics-glossary/genetic-engineering.