Experts Warn Virus Family That Killed 500 Million Could Return As Next Pandemic

Infectious disease experts have raised the alarm that a virus family responsible for one of history's deadliest outbreaks could return to fuel the next global pandemic. Authorities are increasingly concerned that viruses related to the eradicated smallpox, which claimed up to 500 million lives in the 20th century, may exploit waning immunity and evolving biology to re-emerge on the world stage.

Smallpox, caused by the variola virus, was declared eradicated in 1980 after years of global vaccination efforts. But scientists now warn that the family of viruses to which smallpox belongs (the orthopoxviruses) remains a risk, with natural immunity in the population having sharply declined over more than four decades.

Forgotten but Not Gone: A Historic Threat Looms

The world's most devastating viral outbreaks are often taught in history books, yet the spectre of an ancient pathogen returning still haunts scientific circles. Leading epidemiologists have cautioned that the absence of smallpox from global circulation has created an ecological niche that related viruses could exploit, potentially sparking widespread disease.

Researchers point to diseases such as mpox, previously known as monkeypox, as evidence of this threat. Mpox infections surged during a major outbreak in 2022 and have continued to appear internationally in recent years, demonstrating that orthopoxviruses can still transmit amongst humans.

How History Informs Future Risk

Smallpox's historical death toll remains staggering. Prior to its eradication, the virus was amongst the most lethal human diseases, killing hundreds of millions of people worldwide at its peak. Experts warn that although modern medicine has advanced since those tragic decades, complacency could be dangerous.

Orthopoxviruses like mpox, camelpox, buffalopox, and borealpox are not eradicated and circulate naturally in animal reservoirs. When they spill over into human populations, they can cause outbreaks of varying severity.

Professor Fiona Lawrence, an infectious disease specialist at a leading UK university, said: 'The disappearance of smallpox has inadvertently lowered immunity to related viruses. That doesn't mean the risk will materialise tomorrow, but it means vigilance is essential'. Her view echoes global health authorities' long-standing advice: pathogen surveillance and vaccine readiness are crucial to future pandemic preparedness.

Why Mpox Concerns Scientists

The mpox virus drew international attention after causing sustained human outbreaks in 2022 and 2023, with cases identified outside its historically endemic regions. Whilst most infections are not fatal, some forms can be serious, particularly in vulnerable adults, children, and immunocompromised individuals.

Health officials stress that existing vaccines developed originally for smallpox offer some cross-protection against mpox, but they were not designed for widespread modern campaigns. As a result, public immunity is patchy.

Dr Gregor Sinclair, a virologist based in Edinburgh, explained: 'We have good vaccines, but global coverage is uneven, and long-term protection wanes. Viruses in this family have the biological potential to adapt, and human exposure is increasing as we interact more with wildlife'.

This combination of declining immunity and ecological change (such as human expansion into new habitats) creates conditions in which dormant or neglected pathogens might find opportunities to spread more widely.

Preparedness Remains Key

Public health experts stress that this warning is not intended to sow panic, but to urge preparation. The modern world has tools that past generations lacked — from advanced diagnostics to rapid vaccine development — but the window between detection and widespread transmission can be narrow.

Recent pandemics like COVID-19 have shown how quickly a virus can jump continents, disrupt health services and alter daily life. Professor Lawrence added: 'We can't predict exactly which virus will cause the next pandemic, but history teaches us that ignoring risk factors until they become emergencies is costly. Preparedness, including monitoring, vaccines and public health infrastructure, saves lives'.

International bodies such as the World Health Organization continue to monitor orthopoxviruses and other potential threats.

Lessons from the Past

The cautionary message from scientists underscores a broader lesson: infectious disease threats evolve, and so must humanity's response. From the devastating influenza outbreaks of the early 20th century to the recent global experience with COVID-19, each pandemic has revealed vulnerabilities and spurred innovation.

In the interconnected 21st century, a pathogen can circle the globe in hours. The memory of 500 million lives lost serves both as a tribute to those victims and a reminder that vigilance, science, and cooperation are the world's best defence against future outbreaks.