One by one, the viruses have slipped from their hiding places in nature to threaten global populations — SARS, MERS, Zika.
In each case, scientists have scrambled to identify the viruses and to develop vaccines or drugs to stop their spread. After each crisis, the assessment has been the same: Countermeasures were not ready in time to help in the containment effort.
"Always too late," said Jonna Mazet, a scientist at the University of California, Davis, who is keen to break the bugs' winning streak. "We need to think about something different."
Mazet is a key player in an ambitious endeavor called the Global Virome Project, which has proposed cataloguing nearly all of the unknown viruses lurking in nature around the world. In a nutshell, Mazet and other experts want to search out mystery threats before they find us.
The idea has been around for a while and is supported by individual scientists and organizations including the U.S. Agency for International Development, the nonprofit EcoHealth Alliance, HealthMap, ProMED, and the epidemic risk firm Metabiota.
Now support for a global push may be picking up momentum, as scientists and health organizations find themselves repeatedly called upon whenever new threats arise.
The World Health Organization has launched a project called the R&D Blueprint, to spur development of countermeasures for the diseases the agency believes pose the most critical risk, including Crimean-Congo hemorrhagic fever.
A group of powerful players — the World Economic Forum, the Bill and Melinda Gates Foundation, and the Wellcome Trust — have rallied to form an organization called the Coalition for Epidemic Preparedness Innovations, with the goal of finding ways to help fund the creation of vaccines that are badly needed but not likely to turn a profit for drug makers.
And a pilot project that has been underway for the past seven years — called PREDICT — has discovered about 1,000 new viruses.
The Global Virome Project, a nascent effort being driven by a community of interested scientists, would be an extension of this type of work. The approach, they believe, may be more critical now than ever.
A surging global population — encroaching on the natural settings where these viruses exist — is increasing the rate at which these threats emerge, said Dennis Carroll, director of the global health security and development unit at USAID.
"What we're doing today is the same thing we were doing a decade ago, which is the same thing we were doing a decade before that. But we do it and keep expecting the result to be different," he said.
"If we keep pursuing that approach, we will ultimately have a global catastrophe."
Using mathematical modeling approaches, scientists have estimated there may be about 1.3 million undiscovered viruses in the world — "plus or minus," Carroll said. Of those, about a half million may be zoonotic — viruses that can jump from an animal species to infect and spread among people, Mazet said.
Planners of the Global Virome Project have estimated it would cost about $3.4 billion to locate and gather at least preliminary information on 99 percent of those unknown viral threats. (The other 1 percent are so rare that setting out to find them too could nearly double the cost of the effort; no one seems to be pushing for that at this point.)
Carroll told STAT that the pilot study conducted for the project convinced him $3.4 billion is an overestimate, but he didn't want to cite a new figure.
While that cost might seem steep, in some contexts it may appear less so. The Human Genome Project — the landmark project to map the human genome — is estimated to have cost $2.7 billion in 1991 dollars. Using the same gauge, the Global Virome Project would cost about $1.9 billion.
Money aside, is the project doable, or worth doing?
Mazet said that question hung in the air when groups in the effort and thought leaders in the field from around the world gathered over the summer at the Rockefeller Foundation's conference center in Bellagio, Italy.
"There were … sideways glances about whether this was going to be worth it when we had our first 15-minute discussion," she said. "By the end of the couple of days that we were there, 100 percent of the people in the room had decided to sign on and volunteer their time to help govern the effort."
"I'm not going to say everybody said: 'This is the most important thing we could do.' But I've not heard anyone say: 'Wow, we just don't need that information.'"
Michael Osterholm wasn't at the Bellagio meeting. But if the director of the University of Minnesota's Center for Infectious Diseases Research and Policy had been there, he probably would have raised a skeptical hand.
"I wouldn't sit here and say, 'Such studies shouldn't be done,' but I still fail to see at this point how it's going to better prepare the human race for the next infectious disease that jumps from animals to humans," Osterholm said, wondering how would one hear the signal through the static so much data would create.
Others involved in the work have suggested the possibility of drawing up watch lists of viruses based on various factors. How many species can a virus infect, and is there any proof it can jump to people? How close, from an evolutionary point of view, are its natural hosts to people? How often and under what circumstances do people come into context with these animals and their viruses?
"If you're finding it in bat guano and that's at a bat guano farm that's going directly on crops, we're worried," Mazet said.
USAID funds PREDICT, the ongoing pilot project. Now being held up as a proof-of-concept study, researchers are currently working in 30 countries to try to identify new viruses. They take samples — feces, urine, saliva — from wild and domestic animals that have contact with people, and from people themselves. Mazet said so far upward of a quarter million samples have been collected from 74,000 sources.
In the Global Virome Project, the research would be conducted in cooperation with the governments in countries in which the study would be undertaken.
Work like this inevitably raises concerns about who owns what is found and who should share the benefits if a drug or vaccine is made to protect against a virus uncovered in this search — questions that have plagued the emerging infections field in the past.
About a decade ago, Indonesia refused to let outside scientists study H5N1 bird flu viruses circulating there because it learned after the fact that an Indonesian virus was being used to create an experimental human vaccine. And the decision by Dutch researchers to patent the MERS virus when they first identified it in a specimen from the first known case soured Saudi Arabia on cooperating with international researchers.
"Intellectual property, ethics, equity — all those are the most important things to get started," Mazet said. "If we get off on the right foot, this can be done. If we get off on the wrong foot, it can't."
But beyond finding lots of stuff, what could the project do?
When Mazet and other experts described the idea to researchers at a conference in Boston earlier this autumn, several well-informed listeners noted knowing a threat exists isn't enough to prepare. After all, the world first learned about Zika in 1947, but was caught completely flat-footed when the virus started spreading in Brazil, leaving tragically deformed infants in its wake.
Likewise, the first Ebola outbreak occurred in 1976. But there was still no licensed vaccine when, in 2014, the virus ignited a massive epidemic in a part of Africa where Ebola hadn't previously been seen to spread.
Prior knowledge doesn't ensure preparation.
"Even if you did know something and you said, 'Well, this might be one of the top 10 to 20 viruses,' what are you going to do?" asked Osterholm. "Are you going to make a vaccine for it? If you are, how far are you going to take it in terms of pre-licensure studies? How are you going to do surveillance in human populations to detect the virus transmission much sooner than if it just showed up as a human disease?"
Mazet said she doesn't believe the major driver of the work ought to be trying to figure out what emergency vaccines should be in the development pipeline. But knowing where viruses are and how we might interact with them could help us avoid the need for vaccines.
For instance, knowing that the risk of contracting viruses carried in a species of bats is highest when their offspring are young might push ecotourism operators to avoid caves at those times.
And Carroll said filling in more of the picture of the viral world will simply help scientists understand its patterns and interactions better. Right now, predictions are based on the behaviors of a few hundred known viruses, he said.
The idea, Carroll suggested, is to "let data drive a much more robust line of investment against risk, not just what it is that's kicking the door in at the moment."
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