Scientists Observe Early Stages of Pandemic Formation

For the first time in human history, scientists can observe, in near real-time, the molecular processes by which ordinary animal viruses transform into potential pandemic pathogens. Advances in genomic sequencing, computational modeling, and environmental surveillance have opened an extraordinary window into the mechanics of pandemic formation — and what researchers are seeing is both illuminating and deeply alarming.

The question is no longer whether the next pandemic will come. It is whether humanity can decode the warning signs fast enough to stop it.

The Anatomy of a Pandemic: Reassortment, Mutation, and Spillover

Pandemics do not erupt spontaneously. They are built, piece by piece, through a series of evolutionary steps that scientists are only now learning to track. At the molecular level, the most dangerous mechanism is viral reassortment — a process in which two different viral strains infect the same host cell and swap genetic segments, producing an entirely new hybrid virus [1].

Recent breakthroughs in bioinformatics have given researchers powerful new tools to trace these events. A framework called FluRPId, developed by researchers at Oxford, can now identify reassortment patterns based on the genetic diversity of influenza viruses, integrating principles of diversity maximization and epidemiological likelihood [1]. Another tool called TreeSort can accurately identify both recent and ancestral reassortment events across datasets containing thousands of influenza genomes [2].

What these tools have revealed is staggering. The H5N1 clade 2.3.4.4b — the strain currently driving a global panzootic outbreak — underwent approximately three reassortment events over four years for each individual strain between 2020 and 2023 [1]. That represents an extraordinarily high rate of genetic recombination, producing a constellation of new viral genotypes at a pace that has caught even seasoned virologists off guard.

Beyond reassortment, viruses also gain pandemic potential through point mutations that enhance their ability to bind to human receptors, replicate in human cells, or evade the immune system. A 2025 study documented the specific adaptive mutations driving avian-to-human infection in H5N1, mapping the molecular changes that could enable sustained human-to-human transmission [3].

The third pathway — zoonotic spillover — is the moment a virus makes the leap from animal to human. Research shows this is not a random event but is driven by biological prerequisites including host range expansion, viral mutation, and recombination occurring in intermediate hosts [4].

H5N1: A Case Study in Pandemic Formation

If scientists wanted a live demonstration of how pandemics are made, they could hardly ask for a better example than the current H5N1 situation.

In early 2024, H5N1 was detected in U.S. dairy cattle — an event that stunned the scientific community. "This was to everyone's astonishment," researchers noted, describing a situation in which a large proportion of consumer milk in the United States at any given time contained genetic material from highly pathogenic avian influenza viruses [5]. The virus had jumped from wild birds to poultry, then to cattle, then to farmworkers — precisely the kind of cascading cross-species transmission chain that precedes pandemics.

Since April 2024, 70 human cases of avian influenza A(H5) have been reported in the United States, including 41 cases from dairy cattle exposure and 26 from infected poultry contact [6]. One person died in Louisiana in January 2025 — the first U.S. H5N1 fatality, caused by a D1.1 genotype strain associated with more severe illness [6].

"It's completely out of control," scientists warned in a BBC Science Focus analysis, noting that the virus's high levels of cross-species circulation dramatically increase the odds of it evolving both high transmissibility and high lethality [5]. A 2025 study from Indian researchers calculated that once a pandemic strain begins spreading among humans, the window for effective containment could be as narrow as 2 to 10 days [7].

Human-to-human transmission of H5N1 has not yet been confirmed in the United States [6]. But the CDC is monitoring the situation closely, and the virus continues to mutate with each new host species it infects.

Source: CDC / Bird Flu Situation Summary

Data as of Jun 30, 2025CSV

The Accelerating Drumbeat of Spillover Events

H5N1 is not an isolated case. Research published in BMJ Global Health demonstrates that zoonotic spillover events have been increasing at a rate of 4.98% annually, with related deaths climbing 8.7% per year — figures that exclude COVID-19 [8]. If these trends continue, the world could face four times as many spillover events and 12 times as many deaths by 2050 compared to 2020 [8].

The drivers are well understood: deforestation, urbanization, intensive livestock production, wildlife trade, and anthropogenic climate change [9]. A 13-year study of 795 municipalities in the Brazilian Amazon found that a 10% increase in deforestation led to a 3.3% increase in malaria rates [10]. Climate change is extending the geographic range of disease vectors like mosquitoes, while habitat destruction forces wildlife into closer proximity with humans and domestic animals [9].

Approximately 60–75% of emerging human pathogens are zoonotic in origin [4]. The economic toll has been devastating — an estimated annual loss of $212 billion since 1918 [8]. And the reservoir of potential threats is vast: scientists estimate a minimum of 320,000 viruses in mammals await discovery, with roughly half potentially capable of infecting humans [11].

In June 2025, researchers in China announced the discovery of two new bat viruses "dangerously similar" to Nipah and Hendra, alongside 20 other previously unknown viruses found in bat kidneys [11]. Separate research in southern China identified 63 vertebrate-associated viruses in small mammals, including 34 entirely novel species [11].

Watching the Water: The Surveillance Revolution

One of the most promising developments in pandemic preparedness is the emergence of wastewater-based epidemiology as a frontline surveillance tool. What began as a COVID-era improvisation has matured into a sophisticated early warning system capable of detecting pathogen spread days before clinical symptoms appear [12].

Wastewater surveillance can now provide variant-specific, community-representative snapshots of disease prevalence, capturing asymptomatic cases that traditional clinical testing misses entirely [12]. A groundbreaking 2025 study in Nature Medicine proposed global aircraft-based wastewater surveillance networks, demonstrating that just 10 to 20 strategically placed sentinel sites at major airports could provide actionable early warning of pathogen spread across international borders [13].

The WHO's Strategic Plan now promotes integrating surveillance for influenza, coronaviruses, and other respiratory threats into routine health systems using multi-pathogen platforms, genomic sequencing, and wastewater monitoring [14]. A new National Health Emergency Alert and Response Framework aims to detect outbreaks within 7 days and complete early response actions within 14 days [14].

The 100 Days Mission and the Vaccine Library

Even as surveillance capabilities improve, the scientific community is working to compress the timeline between pathogen identification and vaccine deployment. The Coalition for Epidemic Preparedness Innovations (CEPI) is leading the "100 Days Mission" — an ambitious goal to produce safe, effective vaccines within 100 days of identifying a pandemic pathogen [15].

Central to this effort is the construction of a vaccine library: a collection of prototype vaccines targeting the viral families most likely to produce pandemic threats, including Paramyxoviridae, Flaviviridae, Togaviridae, Filoviridae, and others [15]. When a new pathogen emerges, its genome can be rapidly mapped against the library, accelerating vaccine manufacturing and rollout.

CEPI's rapid response framework specifically targets the bottlenecks that slowed COVID-19 vaccine production: clinical trial site readiness, manufacturing scale-up, and regulatory coordination [16]. Their 2027–2031 strategy envisions disease-agnostic trial sites capable of adapting to any pathogen on short notice [15].

Source: World Bank Open Data

Data as of Feb 24, 2026CSV

A Global Agreement — With Gaps

In May 2025, the World Health Assembly adopted the historic WHO Pandemic Agreement, the first legally binding international framework for pandemic prevention, preparedness, and response [17]. The agreement commits nations to rapidly sharing biological materials and genetic sequence data when a potential pandemic pathogen is identified, and to ensuring equitable access to vaccines, diagnostics, and treatments [17].

A critical component is the Pathogen Access and Benefit-Sharing (PABS) system, which requires countries to share pathogen samples and genomic data with WHO-designated laboratories while ensuring that resulting medical countermeasures are distributed fairly to low- and middle-income countries [18].

However, the agreement was adopted in the absence of the United States, and the operational details of the PABS system have been deferred to a separate annex, still under negotiation and expected to be finalized by May 2026 [18]. Without these specifics — and without the world's largest health spender at the table — the agreement's practical impact remains uncertain.

The Preparedness Paradox

Six years after COVID-19 triggered a global alarm, the WHO posed the uncomfortable question: "Is the world better prepared for the next pandemic?" [14]. The answer appears to be a qualified and fragile yes — better in some ways, worse in others.

On the positive side, the pandemic spurred real advances: mRNA vaccine platform technology, wastewater surveillance networks, the WHO Pandemic Agreement, and genomic sequencing capacity have all expanded dramatically. When Sudan virus disease emerged in Uganda in January 2025, WHO facilitated the launch of a clinical trial for a new candidate vaccine within four days [14].

But serious vulnerabilities persist. A series of outbreaks in 2025 — including mpox, H5N1, Ebola, Marburg, Rift Valley Fever, Chikungunya, and measles — exposed persistent weaknesses in early detection, coordination, and access [14]. As of October 2025, 102 disease outbreaks with human transmission were identified in 66 countries [19]. A 2025 report from the International Panel for Pandemic Preparedness warned that pandemic preparedness is "slipping just as global risks grow" [20].

The disparities in preparedness spending are stark. The United States spends over $12,500 per capita on health annually, while India spends roughly $82 [21]. These gaps mean that the countries most likely to experience the early stages of zoonotic spillover — often in tropical regions with rich biodiversity and rapid land-use change — are precisely those least equipped to detect and contain them.

What Scientists Are Watching Now

Beyond H5N1, experts have identified several viral families and specific pathogens that could trigger the next pandemic. The concept of Disease X — an unknown pathogen with pandemic potential — remains central to preparedness planning. Scientists believe the next major threat is most likely to emerge from one of approximately 25 viral families already known to infect humans [22].

The watch list for 2026 includes [22]:

• H5N1 avian influenza — monitoring for mutations enabling human-to-human transmission
• Nipah and Hendra-like viruses — newly discovered strains in bat populations
• Novel coronaviruses — continued surveillance following COVID-19
• Filoviruses — Ebola and Marburg continue to cause outbreaks in Africa
• Arboviruses — dengue, Zika, and chikungunya expanding into new territories due to climate change

Machine learning is now being deployed to predict which reassortment events are most likely to produce human-adaptive strains. A 2025 study in Frontiers in Microbiology used computational methods to predict human-adaptive influenza A virus reassortment based on intersegment constraints, offering a potential tool for flagging dangerous viral combinations before they emerge in nature [23].

The Race Against Evolution

The story of pandemic formation is, at its core, a story about the collision between viral evolution and human activity. Every acre of forest cleared, every new factory farm built, every degree of warming extends the frontier where animal viruses encounter human hosts. And viruses evolve far faster than human institutions can adapt.

Yet the scientific community's ability to observe these processes in real time represents a genuine paradigm shift. For the first time, researchers can watch reassortment unfold, track mutations as they accumulate, and detect new pathogens in sewage before a single patient visits a doctor. The question is whether this knowledge will translate into action — or whether it will simply provide a clearer view of the next catastrophe as it approaches.

The window for prevention is measured in days, not years. The tools exist. The science is advancing. What remains to be seen is whether the political will and global coordination can keep pace with the viruses.