Scientists estimate that there is a minimum of 320,000 viruses in mammals awaiting discovery. Collecting evidence of these viruses, or even a majority of them, they say, could provide information critical to early detection and mitigation of disease outbreaks in humans. This undertaking would cost approximately $6.3 billion, or $1.4 billion if limited to 85% of total viral diversity -- a fraction of the economic impact of a major pandemic like SARS.

Close to 70% of emerging viral diseases such as HIV/AIDS, West Nile, Ebola, SARS, and influenza, are zoonoses -- infections of animals that cross into humans. Yet until now, there has been no good estimate of the actual number of viruses that exist in any wildlife species.

"Historically, our whole approach to discovery has been altogether too random," says lead author Simon Anthony, D.Phil, a scientist at the Center for Infection and Immunity (CII) at Columbia University's Mailman School of Public Health. "What we currently know about viruses is very much biased towards those that have already spilled over into humans or animals and emerged as diseases. But the pool of all viruses in wildlife, including many potential threats to humans, is actually much deeper. A more systematic, multidisciplinary, and One Health framework is needed if we are to understand what drives and controls viral diversity and following that, what causes viruses to emerge as disease-causing pathogens."

"For decades, we've faced the threat of future pandemics without knowing how many viruses are lurking in the environment, in wildlife, waiting to emerge. Finally we have a breakthrough -- there aren't millions of unknown virus, just a few hundred thousand, and given the technology we have it's possible that in my lifetime, we'll know the identity of every unknown virus on the planet," adds Peter Daszak, PhD, corresponding author and president of EcoHealth Alliance.

Secrets of the Flying Fox

To address the challenges of describing and estimating virodiversity, a team of investigators from CII and EcoHealth Alliance began in jungles of Bangladesh -- home to the flying fox. These bats are the largest flying mammal with a wingspan of up to 6 feet; they are also the source of several outbreaks of Nipah virus. The team collected 1,897 biological samples from the animals, which were captured and released. Back in the lab, they used polymerase chain reaction to identify 55 viruses in nine viral families. Of these, only five were previously known, including two human bocaviruses, an avian adenovirus, a human/bovine betacoronavirus, and an avian gammacoronavirus. Another 50 were newly discovered, including 10 in the same family as Nipah. Next the researchers adapted a statistical technique from the field of ecology to estimate that there were another three rare viruses unaccounted for in the samples, upping the estimate of viruses in the flying fox to 58. Finally, this number was extrapolated to all 5,486 known mammals, yielding a total of at least 320,000 viruses.

A Relative Bargain

The researchers then repeated the exercise for cost, extrapolating from an estimated $1.2 million for surveillance, sampling, and discovery of all 58 flying fox viruses to come up with a total of $6.3 billion for all mammals. Given the disproportionate cost of discovering rare viruses, they showed that limiting discovery to 85% of estimated viral diversity would bring the cost down to $1.4 billion.

"By contrast, the economic impact of the SARS pandemic is calculated to be $16 billion," says Dr. Anthony. "We're not saying that this undertaking would prevent another outbreak like SARS. Nonetheless, what we learn from exploring global viral diversity could mitigate outbreaks by facilitating better surveillance and rapid diagnostic testing."

"If we know what's out there, we'll be a lot better prepared when a virus jumps over into a human population," Dr. Anthony continues, adding that prevention is crucial when it comes to viral infections since antivirals are notoriously difficult to develop.

Plumbing the Depths of the Zoonotic Pool

A continued systematic effort to discover mammal viruses would provide a more accurate estimate on total number of viruses in what co-author Stephen Morse, PhD, co-director of the PREDICT Project and professor of Epidemiology at the Mailman School, calls the "zoonotic pool" of potential viral pathogens that threaten humans.

The researchers say the initial estimate of 320,000 is just a starting point and will likely be considerably higher after accounting for additional viral families and employing high throughput sequencing methods developed at CII. They also point to several unknowns, including whether or not the samples from flying foxes in Bangladesh are representative of all flying foxes, which range across Southern Asia; whether or not all mammal species harbor a similar number of viruses; and the extent to which viruses are shared from species to species (as seen with the human, bovine, and avian viruses in the flying fox). Furthermore, the cost of collecting samples could vary depending on habitat (the flying fox expedition in Bangladesh was relatively low compared with similar undertaking for an animal living in more remote areas).

To help fill in some of these blanks, the team is repeating the process in two follow-up studies -- one in a species of primates in Bangladesh in order to see if their viral diversity is comparable to the flying fox's, and another in Mexico, where analysis of samples from six species of bats that share the same habitat will be undertaken to determine the extent to which they share viruses. With additional resources, they hope to expand the investigation to other species and viral families.

"To quote Benjamin Franklin, an ounce of prevention is worth a pound of cure," says senior author W. Ian Lipkin, MD, director of CII. "Our goal is to provide the viral intelligence needed for the global public health community to anticipate and respond to the continuous challenge of emerging infectious diseases."

In fact, this type of large-scale zoonotic virus discovery and characterization is now being done in an economically efficient way through the PREDICT Project, funded by the United States Agency for International Development (USAID). The work described in the study has been integral to the Project's success.

"PREDICT has already discovered more than 240 novel viruses throughout the world in areas where people and animals live in close contact and depend on the same natural resources," says study co-author Jonna Mazet, PhD, director of the UC Davis One Health Institute and co-director of PREDICT. "That includes new coronaviruses, like the ones that cause SARS and the new Middle East Respiratory Syndrome."

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The current study follows the One Health approach, which considers the interdependence of the health of people, animals, and the environment. It is a multidisciplinary collaboration between 21 molecular virologists, ecologists, veterinarians, and mathematicians from institutions, including the Center for Infection and Immunity at Columbia's Mailman School; EcoHealth Alliance, National Autonomous University of Mexico, University of California, Davis; International Centre for Diarrhoeal Disease Research, Dhaka (Bangladesh); Princeton University; National Institutes of Health; and Chittagong Veterinary and Animal Sciences University (Bangladesh).

The study, titled "A strategy to estimate unknown viral diversity in mammals," appears in the journal mBio.