By Shannon Osaka

In January 2009, Jonathan Epstein found himself atop an abandoned storage facility in Khulna, Bangladesh, accompanied by journalist David Quammen and a team of veterinarians. Their unusual mission involved capturing bats for research.

This endeavor came over a decade after the Nipah virus first emerged in Malaysia, a virus known for causing severe respiratory issues, brain inflammation, and high mortality rates, ranging from 40 to 75 percent. The initial outbreak in 1998 infected 283 individuals, resulting in 109 fatalities. Researchers eventually traced the virus’s transmission from bats to pigs, prompting the slaughter of over a million pigs to curb its spread. However, Nipah reappeared in various regions globally, claiming numerous lives. Epstein's team aimed to determine if the bats in Bangladesh were potential carriers of the virus capable of infecting humans.

As a veterinarian and disease ecologist with EcoHealth Alliance, Epstein has traveled extensively, tracking viruses that could potentially jump from animals to humans due to urbanization, deforestation, and other human activities. He was instrumental in linking the first SARS outbreak in 2003 to horseshoe bats in China and the 2013 MERS outbreak to camels and bats. He plans to return to China to investigate the origins of SARS-CoV-2, the virus responsible for the current pandemic, with bats again being prime suspects.

“There are always two critical questions,” Epstein noted from his home in Queens. “How did this happen? And could it happen again?”

Research indicates that 60% of emerging infectious diseases, such as COVID-19, originate in domesticated animals and wildlife, particularly bats, rodents, and non-human primates. Scientists estimate there may be as many as 800,000 zoonotic viruses in nature that could potentially infect humans. Interestingly, the animals that harbor these viruses often remain asymptomatic, serving as “reservoirs” for pathogens, allowing viruses to await the opportunity to jump species.

The likelihood of these dangerous jumps is increasing. Human population growth and environmental degradation are bringing people into closer contact with certain species and the viruses they carry.

“Every future viral threat already exists and circulates among these animals,” stated Dennis Carroll, an expert on zoonotic diseases and former head of USAID's emerging threats division. “We're encountering them more frequently, which increases the chances of spillover.”

As COVID-19 spreads, infecting millions globally and resulting in numerous fatalities, officials and analysts are scrutinizing the world’s lack of preparedness. Many questions arise: Should countries maintain larger stockpiles of medical supplies? Should lockdown measures have been implemented sooner?

These inquiries focus on responses post-epidemic, after a virus has successfully jumped from animals to humans (a process termed “spillover”). However, a dedicated group of ecologists, epidemiologists, and veterinarians has spent years addressing pandemics through a proactive lens. Epstein and his colleagues have been testing bats and pigs in various regions, compiling extensive data on viruses to preemptively prevent spillovers into human populations. After all, no outbreak occurs if the virus never crosses over.

In 2005, an avian influenza strain known as H5N1 began spreading in Southeast Asia, raising alarms due to its high fatality rate of roughly 60%. Carroll was involved in USAID’s response at the time, where he focused on more familiar diseases like malaria and tuberculosis. Although H5N1 didn’t escalate into a pandemic, it made Carroll realize the increasing likelihood of deadly pandemics as human populations expanded.

He suspected many more viruses were lurking, waiting for their chance to make the leap to humans. “It was unclear how many viral threats existed in wildlife,” he recalled. “Were we talking about hundreds of viruses or something vastly different?”

This uncertainty spurred the creation of PREDICT, a project designed to identify and catalog viruses before they could spill over into human populations. Launched in 2009, PREDICT involved collaboration with scientists from the University of California, Davis, and EcoHealth Alliance to discover new viruses and their potential for human transmission.

The program, with an annual budget of approximately $20 million, focused on identifying viral “hotspots,” engaging local governments, and surveying key species that could harbor novel diseases. It also trained individuals in over 30 countries, including Sierra Leone, Uganda, and Bangladesh, to capture animals, collect blood samples for testing, and release them back into their habitats.

“This work is labor-intensive,” Carroll remarked. “It’s not about advanced technology; it involves physically capturing bats and rodents.”

Based on PREDICT’s findings, researchers estimate that around 1.67 million undiscovered viruses circulate among mammals and birds, with 631,000 to 827,000 possessing the potential to infect humans.

Fortunately, the majority of these viruses are not likely to cause severe illness. “Most microbial infections in humans are harmless,” Carroll noted, indicating that researchers need only concentrate on those that could be lethal.

Jonna Mazet, PREDICT's global director until last year, reported that their efforts yielded 168,000 samples from both people and animals, uncovering over 900 new viruses, including 160 coronaviruses related to SARS-CoV-2.

However, capturing animals in various environments was just one challenge. The team also sought to understand the various pathways of virus transmission, searching for patterns and behaviors that could facilitate spillover.

The 2013 Ebola outbreak's initial case was traced back to a child in Guinea, who likely contracted the virus after playing near a tree inhabited by bats displaced by environmental destruction. Similarly, the Nipah outbreak in Malaysia was linked to pigs consuming fruit contaminated by bat droppings.

Certain spillover events are predictable and preventable. “Take live animal markets, for instance,” Epstein explained. “Wild animals, especially bats and rodents, are frequently brought into urban areas, where they interact under unsanitary and stressful conditions, increasing the risk of viral transmission.”

Such close contact creates ample opportunities for human exposure. The SARS outbreak in 2003 is believed to have originated from a wildlife market in Guangdong, China, while the novel coronavirus is suspected to have emerged from a market in Wuhan.

Epstein emphasized the importance of culturally sensitive interventions, such as improving hygiene in wildlife markets or prohibiting the sale of wild animals altogether, to reduce the chances of spillover. “This isn’t about imposing Western standards on cultures with established practices,” he clarified.

Some organizations advocate more stringent measures. The World Conservation Society has called for a global ban on wildlife trade due to pandemic risks. Anthony Fauci, the leading infectious disease expert in the U.S., expressed disbelief that, despite the known risks, the trade continues.

However, wildlife trade is just one factor leading to spillover risks. When Epstein and his team were in Bangladesh, they studied a Nipah outbreak linked to locals consuming sap from date palm trees, which was contaminated by bat urine and feces. This incident highlights how human activities, such as deforestation and agricultural expansion, drive wildlife into closer contact with humans.

Over the last century, the global population has surged. During the 1918-1919 Spanish flu pandemic, the population was about 1.8 billion, whereas today it exceeds 7 billion. As human activities have encroached on wildlife habitats, opportunities for viral transmission have increased.

Despite these challenges, Epstein and other scientists believe that simple changes, such as closing wildlife markets or modifying sap collection practices, could significantly reduce spillover risks. “These events are human-created, and knowing that is hopeful because we can change our behaviors,” he asserted. “These pandemics are preventable.”

In September, the PREDICT program's funding ended after two five-year cycles, disappointing many involved. “It was an innovative program that took significant risks to fund, and its cancellation is unfortunate,” commented Peter Daszak, president of EcoHealth Alliance.

However, the decision to end PREDICT was not politically motivated. Despite previous proposals to cut global health funding, Carroll noted that it’s likely that the Trump administration was unaware of the program's existence. Recently, PREDICT received a temporary funding extension to continue identifying potential animal hosts for SARS-CoV-2.

The scientists behind PREDICT have launched the Global Virome Project, aiming to identify all significant viral threats over the next decade at an estimated cost of $1.6 billion.

“It’s costly,” Mazet acknowledged, “but it pales in comparison to the expenses associated with major epidemics, and it’s minuscule compared to the current crisis.”

To illustrate, the U.S. government invested over $2 billion to manage Ebola outbreaks from 2014 to 2016, while the CARES Act, passed to address economic challenges, totaled around $2 trillion. In contrast, the cost of preventing viral outbreaks represents a mere fraction of that expense, according to Epstein.

Although it’s uncertain whether PREDICT could have averted the COVID-19 pandemic, its decade-long efforts did identify 160 new coronaviruses, though none were SARS-CoV-2. While PREDICT did collaborate with a scientist from the Wuhan Institute of Virology, the area was not prioritized for USAID funding, which focused more on Southeast Asia. This does not indicate a failure of the approach, but rather emphasizes the need for broader surveillance.

Carroll believes that the groundwork laid by PREDICT and the Global Virome Project offers a valuable starting point to address the “viral dark matter” present on our planet and serves as a critical measure against potential future pandemics.

Currently, those alerting the world about zoonotic diseases are following stay-at-home orders like everyone else. Many assert that the pandemic should not be viewed as an unpredictable event, as it stemmed from the very spillover they have long warned against. However, witnessing their concerns materialize remains a challenge.

Before the pandemic, the team struggled to capture policymakers' attention amid competing priorities and short-term thinking. “We were sounding the alarm — to our own exhaustion,” Mazet reflected. “We hope the world is finally listening.”