Pandemics are imagined as dramatic events that erupt without warning. However, their origins are far less conspicuous. In most years, scientists identify only two or three viruses that have never before been recorded in humans. That figure has remained consistent since the 1960s, even though advances in surveillance and genomic sequencing have transformed the speed with which pathogens can be detected.
Most viruses never become household names. Some are observed only once before disappearing from view, while others continue to circulate quietly in isolated animal populations or cause sporadic human infections. Only on rare occasions does the discovery of an unfamiliar virus herald an event that reshapes global health. HIV-1, identified in 1983 after years of undetected spread, and SARS-CoV-2, recognised in early 2020, stand apart as reminders that viruses can extend far beyond the laboratory where a pathogen is first identified.
The challenge for virologists and public-health authorities is§ not merely to discover new viruses but to judge which discoveries warrant immediate concern. A newly detected pathogen may represent little more than an isolated spillover from wildlife, or it may possess the characteristics needed to ignite an international health emergency. Distinguishing between those possibilities in the earliest stages of detection has become one of the central questions in infectious disease research. The first weeks of an outbreak often determine whether containment remains feasible or whether a virus gains the opportunity to establish itself across countries and continents.
Recent pandemics have highlighted another important pattern. Although viruses differ enormously in their biology, many of the pathogens responsible for the largest modern outbreaks belong to a single broad group: RNA viruses. Unlike DNA viruses, RNA viruses replicate using genetic material that is inherently more prone to copying errors. Those frequent mutations allow them to evolve rapidly, producing new variants that can adapt to changing environments and host populations. Scientists have catalogued thousands of RNA virus species, and estimates suggest that many more remain undiscovered. However, despite this immense diversity, only 239 are currently known to infect humans, illustrating that the ability to cross the species barrier is a relatively uncommon evolutionary achievement.
Understanding which of those viruses pose the greatest risk has become a systematic endeavour. Researchers at the University of Edinburgh have recently compiled a catalogue designed to identify the pathogens most likely to threaten human populations. Rather than focusing on a single characteristic, the framework considers several biological and epidemiological features simultaneously. The severity of illness caused by a virus is clearly relevant, but virulence alone cannot produce a pandemic. The defining requirement is sustained transmission between people. Without that capacity, even a highly lethal pathogen remains constrained by how often humans encounter its animal host.
Transmission itself can occur through multiple routes. Some viruses spread through direct physical contact; others through respiratory droplets and aerosols; while others rely on exposure to contaminated blood, bodily fluids, or faecal matter. Certain pathogens depend on mosquitoes or ticks to move between hosts. Each pathway presents different opportunities and limitations, shaping the speed and geographical extent of any outbreak. What matters is whether a virus can maintain uninterrupted chains of infection within human populations rather than repeatedly returning to animal reservoirs.
By that standard, most viruses currently known to infect humans present relatively little pandemic danger. Roughly two-thirds are classified as zoonotic infections that are acquired from animals but rarely, if ever, pass efficiently from one person to another.
Rabies is one of the examples. Tens of thousands of people die from rabies each year following bites from infected animals, yet documented transmission between humans is extraordinarily rare. The virus has persisted for centuries without evolving into a pathogen capable of sustaining widespread human outbreaks, demonstrating that repeated opportunities for adaptation do not necessarily produce greater transmissibility.
The possibility that a zoonotic virus could eventually acquire efficient human-to-human transmission nevertheless remains a persistent concern. Highly pathogenic avian influenza has become a prominent focus of surveillance because repeated spillover events provide opportunities for evolutionary change. However, the historical evidence offers an important cautionary note against assuming that such transitions are inevitable.
There is no documented example of an RNA virus that subsequently evolved into a virus capable of sustained transmission between people. This distinction has practical implications. While vigilance over animal viruses remains essential, the greater immediate threat often lies elsewhere.
Viruses that already possess the ability to spread among humans deserve particular scrutiny because they have already overcome the most formidable evolutionary hurdle. Once sustained transmission is established, further adaptation can enhance efficiency rather than create it from scratch.
SARS-CoV-2 illustrated this process, with successive variants becoming increasingly transmissible after the virus had already entered human populations. Many familiar childhood infections, including measles, mumps and rubella, are thought to have followed similar evolutionary trajectories in the distant past.
Each originated from animal viruses that had already acquired the capacity for human transmission before becoming permanently established within human communities.
Between these highly transmissible pathogens and strictly zoonotic viruses lies another category of particular epidemiological importance.
Some viruses spread from person to person but generate only small, self-limiting outbreaks because their basic reproduction number, or R, remains too low to sustain prolonged transmission. Infection chains eventually burn out without extensive intervention. However, this apparent limitation can prove temporary.
Changes in population density, travel patterns, or environmental conditions may increase opportunities for transmission sufficiently to alter the trajectory of an outbreak. The West African Ebola epidemic of 2014 demonstrated how a virus previously associated with isolated rural outbreaks could behave differently once it reached densely populated urban centres. The underlying biology of the virus had not necessarily changed dramatically; the context in which transmission occurred had.
Experience suggests that this intermediate group has considerable predictive value. Only a few dozen viruses have historically been classified as pathogens capable of limited human transmission. However, many have subsequently caused substantial epidemics. Zaire ebolavirus, chikungunya virus, Zika virus, Oropouche virus and mpox all emerged from this relatively small pool before producing outbreaks that attracted international concern.
More recently, attention has turned to viruses that remain comparatively unfamiliar outside specialist circles. Andes hantavirus, for example, was linked to a recent outbreak on a cruise ship, while Bundibugyo ebolavirus continues to circulate in parts of central Africa. Their appearance illustrates that emerging infectious threats are not confined to pathogens already well known to the wider public.
Nevertheless, not every virus responsible for a regional outbreak possesses the characteristics required for a global pandemic. Close evolutionary relationships provide valuable clues. Viruses capable of efficient human transmission are frequently related to others with similar properties, even if each emerged independently from animal hosts.
SARS-CoV-2 exemplified this principle. Although genetically similar to the virus responsible for the 2002–03 SARS outbreak, it appears to have entered humans through a separate zoonotic event, involving bats, either directly or indirectly. This resemblance explains why coronaviruses resembling SARS had already featured prominently in pandemic preparedness planning before COVID-19 emerged.
The World Health Organisation had identified a SARS-like coronavirus as a plausible candidate for the hypothetical “Disease X,” reflecting growing recognition that this family possessed many of the biological characteristics associated with pandemic potential.
The same reasoning helps explain why some newly detected viruses generate less alarm than others. Neither Andes hantavirus nor Bundibugyo ebolavirus currently exhibits the profile expected of a pathogen capable of sweeping rapidly across the globe. A newly discovered virus closely related to measles, by contrast, would command immediate international attention because it would belong to a lineage already proven capable of exceptionally efficient human transmission. Such a discovery would raise the prospect of a crisis that could surpass COVID-19 in scale, particularly if existing population immunity offered little protection.
One lesson, however, transcends the specific identity of any individual virus. Time consistently favours pathogens over public health systems. Both COVID-19 and recent outbreaks involving Andes hantavirus and Bundibugyo ebolavirus circulated for weeks before being recognised. Delays in detection provide opportunities for transmission, complicate containment efforts and increase the eventual human and economic costs.
As surveillance technologies improve and international collaboration expands, the greatest benefit may lie not simply in discovering more viruses but in understanding them quickly. Earlier recognition of a pathogen’s capacity for human transmission could shorten the interval between emergence and intervention, reducing the advantage that pandemic viruses have historically enjoyed.
In an interconnected world where infectious diseases travel faster than ever before, that head start may prove the difference between an isolated outbreak and the next global health emergency.
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