What If Smallpox Was Never Eradicated?

The Actual History

Smallpox stands as one of humanity's most devastating diseases, with roots stretching back at least 3,000 years. This highly contagious viral infection, caused by the variola virus, killed approximately 30% of those infected and left survivors permanently scarred, often blind, and socially stigmatized. In the 20th century alone, smallpox claimed an estimated 300-500 million lives worldwide, exceeding the death toll of all century's wars combined.

The path toward eradication began with Edward Jenner's pioneering work in 1796, when he demonstrated that inoculation with the milder cowpox virus could provide immunity against smallpox. This breakthrough led to the development of the world's first vaccine. However, global eradication remained a distant dream for nearly two centuries as the disease continued to devastate populations worldwide.

In 1959, the World Health Organization (WHO) initiated a global smallpox eradication campaign, but progress remained limited. The turning point came in 1966 when the WHO launched an intensified effort—the Intensified Smallpox Eradication Program—with an annual budget of $2.4 million and the goal of eliminating smallpox within a decade. Led by American epidemiologist Dr. D.A. Henderson, this campaign adopted a strategy of "surveillance-containment" rather than attempting to vaccinate entire populations. Teams would identify new outbreaks, isolate cases, and vaccinate everyone in surrounding areas, effectively creating a firewall to prevent transmission.

By 1971, smallpox had been eliminated from South America, followed by Asia (including India, where the disease had been particularly persistent) by 1975. The last naturally occurring case in the world was identified in Somalia on October 26, 1977, when Ali Maow Maalin, a hospital cook, contracted the disease but survived.

After a two-year verification period and searches for any remaining cases, the WHO officially declared smallpox eradicated on May 8, 1980—the first and still only human disease completely eliminated from nature through human intervention. The global campaign cost approximately $300 million and saved countless lives and resources in avoided healthcare costs and human suffering.

Following eradication, smallpox virus samples were retained in only two WHO-approved laboratories: the Centers for Disease Control and Prevention (CDC) in Atlanta, USA, and the State Research Center of Virology and Biotechnology (Vector Institute) in Koltsovo, Russia. Debates about whether to destroy these final samples continue to this day, balancing scientific research needs against the risk of accidental release or bioterrorism.

The smallpox eradication campaign remains one of humanity's greatest public health achievements, demonstrating that with international cooperation, adequate resources, and effective strategies, infectious diseases can be conquered. This success has inspired subsequent eradication campaigns against polio, Guinea worm disease, and other infectious diseases, though none has yet achieved the complete success of the smallpox program.

The Point of Divergence

What if the global smallpox eradication campaign had failed? In this alternate timeline, we explore a scenario where, despite decades of international effort, smallpox persisted in human populations into the 21st century.

The most critical period for our point of divergence occurs between 1975 and 1977, when the last strongholds of endemic smallpox were being eliminated. In our actual history, the last naturally occurring case appeared in Somalia in 1977, following successful elimination in South Asia and East Africa. But several plausible scenarios could have derailed this final success:

One possibility involves the fragile political situation in the Horn of Africa during this period. The Ogaden War between Somalia and Ethiopia broke out in July 1977, just as smallpox elimination efforts were reaching their critical final phase in Somalia. In our timeline, WHO teams managed to continue their surveillance-containment work despite the conflict. However, if the war had escalated further or spread to additional regions, vaccination teams could have lost access to critical areas, allowing smallpox to persist in remote populations.

Alternatively, the divergence might have occurred in India, where the eradication campaign faced enormous challenges before succeeding in 1975. With a population of over 600 million at the time, high population density, and limited healthcare infrastructure in rural areas, India represented perhaps the most difficult smallpox elimination challenge. A more organized religious or cultural resistance to vaccination efforts, or a major disruption in the intensified campaign's funding or leadership, could have allowed smallpox to maintain a persistent reservoir.

A third possibility involves the emergence of a vaccine-resistant variola strain. Viruses constantly evolve, and under the intense selective pressure of a global eradication campaign, a variant with even slightly reduced vaccine susceptibility could have undermined containment efforts at the critical final stage.

In this alternate timeline, we'll explore how any of these factors—or a combination thereof—prevented the complete elimination of smallpox, allowing the disease to persist in isolated pockets before reemerging as a continued global health threat into the 21st century.

Immediate Aftermath

Failure in the Horn of Africa (1977-1980)

In our divergent timeline, the intensifying Ogaden War between Somalia and Ethiopia in late 1977 created insurmountable obstacles for the WHO's eradication efforts. As the conflict expanded, several districts along the disputed border became completely inaccessible to vaccination teams. The Soviet Union's intervention on Ethiopia's behalf in November 1977 further militarized the region, creating refugee movements that inadvertently spread smallpox to previously cleared areas.

By early 1978, rather than celebrating the isolation of the last natural case, WHO officials were documenting new outbreaks in refugee camps spread across Somalia, Ethiopia, and neighboring countries. The surveillance-containment strategy that had proven so effective elsewhere faltered in the face of large-scale population movements and inaccessible conflict zones.

Dr. D.A. Henderson, director of the global eradication program, appealed to both warring nations and their superpower backers for temporary ceasefires to allow vaccination campaigns, achieving limited success. However, these "vaccination corridors" proved insufficient as sporadic fighting repeatedly disrupted containment efforts.

WHO's Crisis Response (1978-1981)

The WHO's announcement in May 1978 that smallpox eradication had suffered a significant setback sent shockwaves through the international public health community. The organization's Executive Board convened an emergency session in Geneva, where a revised strategy was developed with three key components:

Geographical Containment: Intensive vaccination campaigns in all countries bordering the Horn of Africa to prevent further spread
Resource Mobilization: An emergency funding appeal that tripled the eradication program's budget to over $7 million annually
Diplomatic Initiative: United Nations-backed negotiations for humanitarian access to conflict zones specifically for smallpox vaccination

These measures achieved partial success. While smallpox was prevented from regaining a foothold in Asia or spreading extensively in Africa, it established persistent reservoirs in parts of Somalia, Ethiopia, and Sudan, with occasional outbreaks reported in neighboring countries through 1981.

Political Fallout (1980-1983)

What had been positioned as humanity's imminent victory over a disease became a symbol of international cooperation's limitations in the Cold War era. The WHO's 1980 World Health Assembly, which in our timeline celebrated eradication, instead became a forum for recrimination.

American representatives blamed Soviet military involvement for destabilizing the Horn of Africa, while Soviet delegates pointed to Western-backed regimes in Somalia and Sudan as uncooperative with international health authorities. Developing nations criticized both superpowers for prioritizing geopolitical interests over human health.

This diplomatic fallout had tangible consequences for global health governance. The WHO's prestige suffered, affecting its ability to coordinate other international health initiatives. Funding for the Expanded Program on Immunization stagnated as donor nations questioned the feasibility of ambitious disease control targets.

Scientific and Medical Developments (1979-1985)

The continuing threat of smallpox spurred renewed research efforts. In 1979, pharmaceutical companies that had scaled back vaccine production resumed operations, and governments maintained or rebuilt strategic stockpiles. The United States' CDC established the Poxvirus Advanced Research Division in 1980, accelerating work on improved vaccines and antiviral treatments.

A significant breakthrough came in 1982 when researchers at the Pasteur Institute developed an enhanced smallpox vaccine with fewer side effects, making mass vaccination campaigns safer in immunocompromised populations. Simultaneously, Soviet scientists at the Vector Institute pioneered early antiviral compounds showing activity against poxviruses.

Public health schools worldwide continued training specialists in smallpox recognition and containment, unlike our timeline where this expertise began to fade. Epidemiological surveillance systems were strengthened globally, with particular emphasis on early detection technologies that could identify outbreaks before they expanded.

Social Impact and Public Perception (1980-1985)

For populations in regions where smallpox persisted or frequently recurred, the disease remained a dreaded reality affecting daily life. In parts of East Africa, the facial scarring characteristic of smallpox survivors continued to carry social stigma, and families routinely postponed naming ceremonies for newborns until children survived the risk of infection.

In developed nations, smallpox vaccination remained part of standard childhood immunization schedules, despite the rare but serious side effects that claimed approximately one life per million vaccinations. The public perception of vaccination began to diverge significantly from our timeline—the visible threat of smallpox outbreaks counterbalanced emerging vaccine hesitancy movements, keeping public support for immunization programs generally strong.

By 1985, smallpox had settled into a pattern of endemic presence in parts of East Africa with periodic outbreaks elsewhere when containment measures faltered. The world had adjusted to the reality that this ancient disease would remain a permanent challenge rather than a conquered foe—a situation that would significantly shape public health priorities and international relations in the decades to come.

Long-term Impact

Persistent Disease Ecology (1985-2000)

As the 20th century entered its final decades, smallpox established what epidemiologists termed "persistent regional endemicity" across parts of the Horn of Africa and adjacent regions. The disease followed a cyclical pattern: periods of relative containment followed by flare-ups when surveillance weakened or conflict disrupted healthcare systems.

Particularly devastating outbreaks occurred:

During the Ethiopian civil war (1987-1991), when government collapse left vaccination programs unfunded
Following the Rwandan genocide (1994), when the virus spread through refugee populations in eastern Zaire (now Democratic Republic of Congo)
Amid the Second Sudanese Civil War (1983-2005), where religious objections to vaccination complicated control efforts in some southern regions

These persistent reservoirs created a constant global health security threat. High-income nations maintained mandatory smallpox vaccination despite its costs and complications, while middle-income countries experienced periodic importation events requiring expensive emergency responses.

By 2000, global smallpox incidence had stabilized at approximately 50,000-100,000 cases annually, with 10,000-20,000 deaths—dramatically lower than pre-vaccination era rates but still representing significant human suffering and healthcare burden.

Evolution of Public Health Systems (1990-2010)

The continued threat of smallpox profoundly shaped international health systems development. Unlike our timeline, where resources shifted toward other priorities after 1980, in this alternate reality, infectious disease control infrastructure remained robustly funded.

The WHO's budget priorities reflected this focus, with the Division of Communicable Disease Control receiving nearly triple the funding compared to our timeline. This investment yielded several significant developments:

Global Health Surveillance Network: By 1995, a real-time digital disease reporting system connected health facilities across 145 countries, enabling rapid response to outbreaks
Vaccine Innovation: Research funding for thermostable vaccines (resistant to heat deterioration) accelerated, solving a crucial problem for vaccination in tropical regions without reliable cold chains
Biocontainment Infrastructure: High-security BSL-4 laboratories were constructed in every major region by 2005, enhancing diagnostic capacity and pathogen research

The persistent smallpox threat also influenced healthcare workforce development. Medical and nursing education worldwide maintained strong emphasis on infectious disease recognition and management, and epidemiology emerged as a higher-status medical specialty attracting top talent.

Technological and Pharmaceutical Developments (1990-2015)

The continuing battle against smallpox drove significant pharmaceutical innovation. The first effective antiviral treatment, cidofovir, was approved for emergency use in 1996, followed by brincidofovir in 2001 and tecovirimat in 2007. These medications reduced smallpox mortality from approximately 30% to under 10% when administered early in infection.

Vaccine technology also advanced dramatically. The third-generation MVA (Modified Vaccinia Ankara) smallpox vaccine, approved in 1998, eliminated most serious side effects associated with traditional vaccines, making universal vaccination programs safer. By 2010, a recombinant protein-based vaccine provided protection even for immunocompromised individuals who couldn't receive live-virus vaccines.

Diagnostic technology evolved from time-consuming viral cultures to rapid PCR-based tests deployable in field conditions, allowing confirmation of suspected cases within hours rather than days. By 2015, smartphone-coupled diagnostic devices enabled frontline health workers to confirm diagnoses even in remote settings.

These technologies had spillover effects benefiting management of other diseases. The diagnostic platforms developed for smallpox were quickly adapted for influenza, viral hemorrhagic fevers, and novel pathogens, while the vaccination infrastructure strengthened delivery systems for all immunizations.

Geopolitical and Economic Consequences (2000-2020)

The persistent smallpox threat reoriented international relations around biosecurity concerns. The UN Security Council formally classified certain disease outbreaks as potential threats to international peace and security in 2004, establishing the legal framework for intervention in health emergencies regardless of national sovereignty.

Economic impacts were substantial and multifaceted:

Travel and Tourism: Countries with active smallpox transmission faced significant restrictions, with mandatory vaccination requirements for travelers and occasional travel bans during outbreaks
Pharmaceutical Industry: The guaranteed market for smallpox vaccines and antivirals (approximately $4.2 billion annually by 2010) created a stable profit center for several major pharmaceutical companies
Healthcare Costs: High-income countries spent an estimated 0.5-0.7% of healthcare budgets on smallpox prevention, surveillance, and occasional outbreak responses
Productivity Losses: Regions with endemic smallpox experienced reduced foreign investment and measurable productivity losses from illness and quarantine measures

The economic burden fell disproportionately on developing nations, particularly those in East Africa where the disease remained endemic. This disparity contributed to the formation of the Global Health Equity Fund in 2012, which dedicated $1.2 billion annually specifically to smallpox control in endemic regions.

Social and Cultural Dimensions (2000-2025)

Living with the threat of smallpox shaped cultural attitudes toward disease and public health in profound ways. Unlike our timeline, where diseases that leave visible disfigurement became increasingly rare in developed nations, the continued presence of smallpox maintained public awareness of infectious disease consequences.

This awareness influenced various social dimensions:

Vaccine Acceptance: Anti-vaccination movements gained significantly less traction than in our timeline, as the visible threat of smallpox provided constant reminder of pre-vaccine disease burdens
Infectious Disease in Fiction: Disease outbreak narratives remained a prominent genre in literature and film, with smallpox frequently featured as the prototypical deadly contagion
Privacy vs. Public Health: Societies generally accepted more intrusive public health measures, including vaccination requirements for school attendance and employment in most countries
Disability Rights: The presence of individuals with smallpox scarring and blindness strengthened disability advocacy movements, particularly around discrimination in employment and education

By 2025 in this alternate timeline, smallpox has been reduced to fewer than 10,000 cases annually worldwide, concentrated in conflict zones and areas with limited healthcare infrastructure. However, eradication remains elusive, and humanity continues to bear the burden of vaccination, surveillance, and occasional outbreaks—a perpetual reminder that even our most sophisticated medical interventions cannot always completely vanquish diseases that co-evolved with our species.

Expert Opinions

Dr. Maria Sanchez, Professor of Global Health Security at Johns Hopkins University, offers this perspective: "Had smallpox eradication failed in the 1970s, we would be living in a fundamentally different public health landscape today. The psychological impact of that failure would have tempered ambitions for subsequent disease eradication programs, potentially leading to a more pragmatic 'control not conquest' paradigm in global health. Ironically, this might have prepared us better for emerging diseases like HIV, where early unrealistic hopes for quick medical solutions gave way to long-term management strategies. The persistent smallpox threat would have maintained robust infectious disease infrastructure in many countries that, in our timeline, allowed those systems to atrophy until the COVID-19 pandemic exposed the gaps."

Professor Ahmed Osman, Director of the Institute for Infectious Disease History at the University of Nairobi, provides a regional perspective: "The failure to eradicate smallpox would have profoundly altered East African development trajectories. Beyond the direct health burden, the economic stigma associated with being the world's smallpox reservoir would have compounded existing development challenges. However, we shouldn't overlook potential positive counterbalances—the international resources directed toward smallpox control would have built healthcare capacity with benefits for managing other diseases. Countries like Kenya and Uganda might have developed pharmaceutical manufacturing capabilities decades earlier than in our timeline, driven by the need for regional vaccine production. The narrative that Africa is merely a recipient of global health interventions might have shifted toward recognizing African scientists and healthcare workers as essential partners in a continuing global health security challenge."

Dr. William Chen, former Chief of Epidemiology at the World Health Organization, contemplates the scientific implications: "A continued smallpox threat would have dramatically altered our understanding of viral pathogens and approaches to disease management. Genomic surveillance techniques would have likely developed earlier, driven by the need to track variola virus evolution in real time. The tension between disease control demands and laboratory safety concerns would have forced earlier development of sophisticated biocontainment protocols. I suspect we would have seen greater investment in broad-spectrum antivirals rather than the disease-specific approaches that dominated late 20th century pharmaceutical research. Most significantly, the field of bioethics would have grappled much earlier with questions about research on dangerous pathogens, mandatory vaccination policies, and the appropriate limits of public health authority—debates that, in our timeline, remained largely theoretical until recent pandemics forced them into public discourse."