The smallpox virus, known formally as variola, officially exists in only two places on Earth: a high-containment laboratory at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the VECTOR research center in Koltsovo, Russia. These are the only repositories sanctioned by the World Health Organization (WHO) since the late 1970s, when global vaccination campaigns drove smallpox to extinction in the wild. But the full picture is less tidy than that two-site answer suggests, because forgotten vials have turned up in unsecured locations, the virus’s DNA has been recovered from centuries-old remains, and advances in synthetic biology now make it theoretically possible to rebuild the pathogen from scratch.
The Two Official Repositories
After the WHO certified the global eradication of smallpox in 1980, member nations were asked to either destroy their variola stocks or transfer them to one of two designated laboratories. The CDC’s facility in Atlanta and Russia’s State Research Center of Virology and Biotechnology (VECTOR) near Novosibirsk became the sole authorized holders. Both operate at the highest biosafety level, BSL-4, which requires sealed suits, decontamination showers, negative-pressure rooms, and independent air supplies. The WHO periodically sends international inspection teams to both sites to verify that the virus is stored securely and that research conducted on it falls within agreed-upon boundaries.
The arrangement was supposed to be temporary. The WHO has debated destroying those last stocks for decades, and in 2011 it revisited the question yet again. Proponents of destruction argue that keeping live virus around is an unnecessary risk in a world where smallpox no longer circulates. Opponents counter that the virus’s complex biology is far from fully understood and that further research on intact variola could yield better vaccines and antivirals. A 2011 review in Emerging Infectious Diseases laid out the case against destruction, noting that variola has a remarkable ability to manipulate the human immune response through mechanisms scientists were only beginning to unravel and that modern synthetic biology could theoretically recreate the virus anyway, rendering destruction of the remaining stocks symbolic rather than genuinely protective.1PubMed Central. Should remaining stockpiles of smallpox virus (variola) be destroyed? As of today, the WHO has repeatedly postponed a final decision, and both repositories remain operational.
Forgotten Vials and Accidental Discoveries
The two-repository system assumes every sample was accounted for during the consolidation decades ago. That assumption turned out to be wrong. In July 2014, workers at a National Institutes of Health (NIH) facility in Bethesda, Maryland, stumbled upon a handful of vials labeled as containing variola virus. The vials had been sitting in an unsecured storage area, apparently forgotten since at least the 1950s or 1960s. The CDC investigated and confirmed that two of the vials still contained viable virus, meaning the pathogen inside was alive and capable of replicating.2PubMed. Discovery of forgotten variola specimens at the National Institutes of Health in the USA
The NIH discovery was alarming not because anyone was exposed, but because it demonstrated that rogue samples can exist outside official channels, sitting unnoticed for decades. If one of the world’s premier biomedical campuses could lose track of smallpox vials, it raised uncomfortable questions about whether other labs, universities, or old government facilities might harbor similar surprises. The vials were transferred to the CDC and eventually destroyed under WHO observation, but the incident underscored a persistent gap between the official story of two repositories and what might actually be scattered in freezers around the world.
Could Smallpox Survive in the Environment?
One question that comes up whenever people learn about eradication is whether the virus might still be lurking somewhere in nature, perhaps in an old burial ground or sealed building. The short answer is that variola is tough for a virus but not indestructible, and its survival depends heavily on temperature and humidity. Experiments published in the Bulletin of the World Health Organization tested how long the virus lasted in dried scabs stored on raw cotton. In tropical heat (around 30°C), it survived no more than about three to four months. At cooler, temperate temperatures (20–25°C), small amounts of virus could persist for up to 18 months. Under refrigeration at 4–5°C in sealed containers, however, the virus remained viable for ten years or more with little loss of potency.3PubMed Central. Survival of variola virus in raw cotton
Those numbers mean that in ordinary environmental conditions, variola degrades over months, not centuries. A scab in a warm attic or a tropical grave would lose infectivity relatively quickly. But what about permafrost? Corpses of smallpox victims buried in frozen ground in Siberia or Arctic regions have drawn scientific attention precisely because sub-zero temperatures can preserve organic material for extraordinary lengths of time. Researchers have examined well-preserved bodies and historical tissue samples for traces of the virus. While viral DNA has been recovered from some of these specimens, the results so far have not demonstrated that intact, viable virus survives in old remains.4PubMed Central. Poxvirus viability and signatures in historical relics Finding genetic fragments is very different from finding live virus. Still, as permafrost continues to thaw due to climate change, the theoretical risk keeps scientists attentive. The consensus view is that the probability of a viable reemergence from frozen soil is extremely low but not strictly zero.
No Animal Reservoir
Unlike many dangerous viruses, variola has no known animal host. Humans were the only reservoir for smallpox, which is precisely what made eradication possible in the first place. If the virus had been quietly cycling through rodents, livestock, or any other species, wiping it out through human vaccination alone would not have worked.5PubMed. Smallpox: the basics Variola’s extremely narrow host range is a defining feature of the virus, and genetic analyses have explored how it became so specialized.6PubMed Central. Prediction of steps in the evolution of variola virus host range
This is reassuring in one sense: there is no hidden animal population quietly maintaining smallpox the way bats maintain Ebola or certain rodents maintain hantaviruses. But it also means the virus had no fallback. Once the last human infection was prevented, the chain of transmission ended for good in the natural world. The only places variola persists are the ones humans chose to keep it, plus any overlooked samples like the NIH vials.
The Synthetic Biology Problem
Perhaps the most unsettling wrinkle in the “where does it still exist” question is that the virus might not need to physically exist in a freezer to make a comeback. In 2017, a team of Canadian researchers synthesized horsepox virus, a close relative of variola within the same orthopoxvirus family, entirely from scratch using commercially available DNA fragments. The cost was modest and the techniques were well within reach of a competent molecular biology laboratory.7PubMed. The De Novo Synthesis of Horsepox Virus: Implications for Biosecurity and Recommendations for Preventing the Reemergence of Smallpox
The horsepox synthesis sent shockwaves through the biosecurity community. Variola’s complete genome has been sequenced and is publicly available in scientific databases. If someone could build horsepox from ordered DNA, the same approach could in principle be used to reconstruct variola itself. The primary barriers are regulatory and ethical, not technical. This reality has reshaped the debate about destroying the official stocks: if the genome is digital and the tools to assemble it are getting cheaper every year, eliminating the physical samples at the CDC and VECTOR would not eliminate the possibility of the virus being recreated. It would, however, remove the only legal, inspected copies, potentially making the world less prepared rather than safer.
Past Suspicions About Undeclared Stocks
During the Cold War, the Soviet Union ran an extensive biological weapons program that included work with variola virus. Defectors and later investigations revealed that the program produced weaponized smallpox at scales far beyond anything needed for defensive research. When the Soviet Union dissolved, the full accounting of what happened to those stocks remained incomplete. Western intelligence agencies have long worried that samples may have been transferred, sold, or simply lost during the chaotic 1990s. No confirmed evidence of undeclared variola stocks outside the two authorized sites has surfaced publicly, but the lack of full transparency from the Soviet-era program means absolute certainty is impossible.
Beyond the former Soviet Union, concerns have been raised about other nations. The 2001 anthrax letter attacks in the United States, while involving a different pathogen entirely, demonstrated that even supposedly tightly controlled dangerous agents could be misused by individuals with insider access. These episodes collectively make the biosecurity community cautious about treating the two-repository arrangement as airtight. The system relies on trust, compliance, and honest reporting by every nation that once handled variola, and history suggests that trust may not be fully warranted.
Mpox and the Orthopoxvirus Family
Smallpox may be gone from the wild, but its relatives are not. The orthopoxvirus genus includes several members that infect humans, and the most prominent in recent years is mpox virus (formerly called monkeypox). Mpox circulates in parts of Central and West Africa and triggered a global outbreak in 2022 that reached dozens of countries. It causes a disease that resembles a milder version of smallpox, with fever, rash, and sometimes painful lesions, though the fatality rate is far lower.
Because orthopoxviruses are genetically similar, vaccines developed against one tend to offer some protection against others. Smallpox vaccines based on vaccinia virus have been shown to produce antibodies and T-cell responses that cross-react with mpox virus antigens.8The Lancet Infectious Diseases. Mpox vaccine and infection-driven human immune signatures: an immunological analysis of an observational study Studies have estimated that older smallpox vaccines provided roughly 85% protection against mpox.9PubMed Central. The assessment on cross immunity with smallpox virus and antiviral drug sensitivity of the isolated mpox virus strain WIBP-MPXV-001 in China People vaccinated against smallpox during childhood, generally those born before the early 1980s, may still carry some residual cross-reactive immunity, though it fades over time. Research on healthcare workers with a history of smallpox vaccination has confirmed detectable cross-reactive immune responses against mpox.10PubMed. Historic smallpox vaccination and Mpox cross-reactive immunity: Evidence from healthcare workers with childhood and adulthood exposures
This family connection matters for the “where does smallpox exist” question because it means the broader orthopoxvirus threat has not disappeared. Even without variola circulating, related viruses continue to jump into human populations, and the tools developed to fight smallpox remain central to combating these emerging infections.
Vaccines and Antivirals Kept in Reserve
Governments have not simply locked the virus away and forgotten about it. Several countries, particularly the United States, maintain strategic stockpiles of smallpox vaccines and antiviral drugs in case the virus reemerges through bioterrorism, a laboratory accident, or some unforeseen natural event. Two licensed vaccines are available for orthopoxvirus prevention. ACAM2000 is a replication-competent vaccinia vaccine that is highly effective but carries risks of serious side effects, including heart inflammation. JYNNEOS (also known as Imvamune or MVA-BN) uses a modified vaccinia virus that cannot replicate in human cells, giving it a much better safety profile. JYNNEOS demonstrated about 82% effectiveness in preventing mpox during the 2022 outbreak and was recommended by the U.S. Advisory Committee on Immunization Practices as an alternative to ACAM2000.11PubMed Central. Safety and Efficacy of Repurposed Smallpox Vaccines Against Mpox: A Critical Review of ACAM2000, JYNNEOS, and LC1612PubMed Central. Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses
On the treatment side, the antiviral drug tecovirimat (brand name TPOXX) was approved specifically for smallpox, though it has never been tested in actual human smallpox cases for obvious reasons. It works by targeting a protein called F13 that the virus needs to form the type of viral particles that spread between cells and between people, effectively blocking the virus from moving beyond the first cells it infects.13PubMed Central. Tecovirimat: A journey from discovery to mechanistic insights in poxvirus inhibition Tecovirimat has shown broad activity against multiple orthopoxviruses in lab and animal studies, making it a versatile tool in the medical countermeasure arsenal.14PubMed Central. An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications These stockpiles represent a kind of insurance policy, maintaining the ability to respond quickly even though the probability of needing to use them against actual smallpox remains very low.
Detecting the Virus If It Reappears
Because most physicians alive today have never seen a case of smallpox, rapid laboratory diagnosis would be critical in any suspected reemergence. Researchers developed real-time PCR assays specifically designed to detect variola DNA quickly and with high specificity. One assay targeting the orthopoxvirus hemagglutinin gene achieved sensitivity down to roughly 25 copies of viral DNA on widely available testing platforms.15PubMed Central. Real-time PCR assay to detect smallpox virus Another approach using melting-curve analysis can distinguish variola from its close relatives, including cowpox, monkeypox, and vaccinia, based on subtle differences in the DNA sequence, all within a single rapid test.16PubMed Central. Detection of smallpox virus DNA by LightCycler PCR A further assay allows simultaneous identification and differentiation of variola from other pathogenic orthopoxviruses, ensuring that a case of mpox or a vaccinia reaction is not mistaken for smallpox and vice versa.17PubMed. Real-time PCR to identify variola virus or other human pathogenic orthopox viruses
These diagnostic tools sit in reference laboratories around the world, many of them part of the WHO’s Laboratory Network for the Diagnosis of Smallpox. The goal is to be able to confirm or rule out a case within hours rather than days, because early detection would be the difference between containing a localized incident and facing a broader outbreak in a world where routine smallpox vaccination ended over four decades ago.
Why Most People Are No Longer Immune
Routine childhood vaccination against smallpox ended in the United States in 1972 and in most other countries by the early 1980s. That means anyone born after those dates has no vaccine-derived immunity. Even among those who were vaccinated as children, immunity wanes substantially over time. Research on people born before 1981 who received the Chinese vaccinia Tiantan vaccine found that only a minority still had detectable antibodies capable of neutralizing mpox virus decades later.9PubMed Central. The assessment on cross immunity with smallpox virus and antiviral drug sensitivity of the isolated mpox virus strain WIBP-MPXV-001 in China This means the global population is more vulnerable to any orthopoxvirus, including variola, than at any point in modern history. It is a key reason why governments maintain vaccine stockpiles and why the debate over destroying the last official variola samples carries such weight.
The vulnerability is unevenly distributed. Military personnel, certain laboratory workers, and healthcare responders in some countries continue to receive orthopoxvirus vaccination. But the vast majority of the world’s eight billion people have no specific protection. If variola were released today, whether from a laboratory accident, a bioterror attack, or the vanishingly unlikely scenario of a natural reemergence, the initial spread could be rapid before vaccine stockpiles could be deployed. This population-level susceptibility is, in a real sense, the most important context for the question of where the virus still exists. The physical location of the samples matters less than the gap between the virus’s potential and humanity’s current defenses against it.
How Warm Permafrost Factors Into Future Risk
Climate scientists project that large areas of Arctic permafrost will thaw over the coming decades, exposing organic material that has been frozen for centuries. Smallpox killed untold millions across northern regions during epidemics from the 1700s through the early 1900s, and many victims were buried in shallow graves in permanently frozen soil. As that soil warms, the question of whether infectious variola could emerge from these burials becomes less hypothetical. Researchers who have examined historical poxvirus remains have found viral DNA signatures in some samples, confirming that genetic material can persist for a very long time under cold conditions.4PubMed Central. Poxvirus viability and signatures in historical relics But DNA persistence and actual infectivity are different things. A virus needs intact proteins and a functional genome to infect a cell, and freezing and thawing cycles tend to damage those structures over long timescales.
Most virologists consider the risk of a permafrost-derived smallpox reemergence to be remote. The scenario requires not just that the virus survive intact for over a century under imperfect freezing conditions, but also that a person come into direct contact with the remains in a way that allows infection through skin or respiratory exposure. That chain of events is unlikely. Nonetheless, Russian researchers have periodically investigated Siberian burial sites with precisely this concern in mind, and the question is taken seriously enough to be factored into broader biosecurity planning. It is one of those risks that sits at the intersection of climate science and infectious disease, remote in probability but potentially catastrophic in consequence.