As the world reels from a global viral wildfire costing hundreds of thousands of lives and trillions of dollars, epidemiologists are turning their attention to how best to prevent the next pandemic.
Many argue that the wisest use of limited global scientific and financial resources is to focus on surveillance, detection, and intensive study of new diseases as they spill over from the wild into humans. But one infectious disease expert has a more ambitious plan — to sample much of the world’s vast wildlife populations to identify the likely viral culprits that could spark the next pandemic.
It’s a daunting prospect. Scientists have identified only 4,000 of the estimated 1.67 million viruses thought to exist on earth. The goal of Dennis Carroll and his Global Virome Project is, over the next decade, to enlist an international network of scientists to eventually collect hundreds of thousands of those viruses and map their genomes. Carroll estimates the cost of the project at $1.2 billion.
“We know that all future viral threats already exist and they are circulating in wildlife,” Carroll said. “Rather than waiting for that future threat to spill over into us and then become aware of it and react to it, the Global Virome Project is about going out into that population of wildlife and documenting and characterizing what is out there, and then being able to risk-stratify among all of the things you discover — which ones do you need to pay attention to?”
Some infectious disease experts have criticized the Global Virome Project as too broad and expensive.
Carroll, 71, comes to the task well-prepared. In 2009, as head of the Emerging Threats Division of the U.S. Agency for International Development (USAID), he helped create the PREDICT program, which sought to identify what viruses living in wild animals, or in domestic animals that had been infected by wild ones, posed the greatest threat to humans. One of the first large-scale attempts to get ahead of the so-called viral “spillover” of zoonotic diseases into humans, PREDICT identified roughly 1,200 new viruses, trained several thousand people in more than 30 countries, and collaborated with or created 60 laboratories worldwide.
The PREDICT project went dormant in March because of a lack of funding from the Trump administration. But as the coronavirus pandemic worsened, the administration made an emergency allocation of $2.26 million to PREDICT earlier this month to extend the program for six months to help identify the animal sources of the Covid-19 virus.
Carroll launched the Global Virome Project two years ago after leaving USAID. The initiative is now raising funds from governments and foundations and, with promised financial support from the Chinese and Thai governments, was supposed to begin sampling wild animal populations in those countries this year. Those projects have yet to get underway because of the scramble to respond to the Covid-19 pandemic.
Some infectious disease experts have criticized the virome project as too broad and expensive, arguing that such a small percentage of the world’s 1.6 million animal viruses will actually cross into humans and pose a threat that cataloguing hundreds of thousands of viruses is a misguided use of resources. In a 2017 paper, two scientists wrote that a vast atlas of viruses simply wouldn’t head off pandemics and that measures needed to be targeted more at virological surveillance.
“(T)he inconvenient truth for all of those working in the realm of disease emergence is that the vastness of the unknown virosphere and the diverse range of viruses that have achieved endemic transition in humans means that any attempt to predict what virus may emerge next will face substantial and probably crippling difficulties,” Jemma Geoghegan and Edward C. Holmes wrote in Open Biology. Instead they recommended surveillance at the “fault line of disease emergence that is the human-animal interface, particularly those shaped by ecological disturbance.”
Holmes, an infectious disease specialist at the University of Sydney, expressed skepticism about the Global Virome Project in a 2018 commentary in Nature. He wrote that while “broad genomic surveys of animal viruses will almost certainly advance our understanding of virus diversity and evolution … they will be of little practical value when it comes to understanding and mitigating the emergence of disease.”
More important, he said, is rapidly detecting diseases when they cross into humans, discovering the molecular mechanisms that enable a disease to jump between individuals, analyzing how a disease spreads through human populations, and understanding exactly how it infects humans so that effective therapies can be developed.
Carroll said that while detection and surveillance are important and are part of the Global Virome Project, a comprehensive global study of viromes would give epidemiologists a much more detailed picture of the most critical places to train those tools. The project plans to create an algorithm for looking at which viruses are most likely to pose a risk to humans — based on features of the virus and features of the host — coupled with a look at risky practices and places that could lead to the spread of zoonotic diseases (those that move from animals into people).
The virome project’s goal is to collect 70 percent of the world’s 1.67 million viruses.
“In Wuhan, clearly the bringing in of wildlife and mixing them with livestock and exposing them to people while animals are still alive poses enhanced risk,” said Carroll, referring to the animal market in China where the Covid-19 virus is believed to have spilled over into humans. “There are biosecurity measures to reduce the risk of viruses moving into livestock or into people.” He thinks that closing wild animal markets would merely drive the trade underground and make it harder to monitor.
Predicting pandemics is difficult. It involves monitoring some of the world’s remotest regions, where health infrastructures are often non-existent or substandard. When humans disrupt an ecosystem by punching a new road into wild areas, that intrusion can suddenly unleash pathogens that had been circulating only among wildlife. The virus that caused AIDS, for example, came from chimpanzees and probably jumped the species barrier to humans when bushmeat hunters shot and butchered a chimp. Seventy-five percent of emerging infectious diseases that affect humans come from animals, and two-thirds of those come from wild animals.
A large part of the threat is the earth’s burgeoning population of nearly 8 billion people, researchers say, creating countless more exposures to pathogens. “[T]he rate of zoonotic viral spillover into people is accelerating, mirroring the expansion of our global footprint and travel networks, leading to a nonlinear rise in pandemic risk and an exponential growth in their economic impacts,” Carroll and his colleagues wrote in a 2018 Science paper on the Global Virome Project.
“We’ve penetrated deeper into ecozones we’ve not occupied before,” Carroll said. “The poster child for that is the extractive industry — oil and gas and minerals, and the expansion of agriculture, especially cattle. That’s the biggest predictor of where you’ll see spillover.”
In their 2018 paper, Carroll and eight other researchers said the Global Virome Project’s goal was to collect 70 percent of the world’s 1.67 million viruses, the other 30 percent being so rare and difficult to collect that they don’t pose much of a threat. The scientists estimated that 631,000 to 827,000 of the world’s viruses have zoonotic potential, and that an unknown, smaller number would cause pathology.
Amesh Adalja, an expert on infectious diseases at the John Hopkins University Center for Health Security, said that in the case of deadly viruses like Covid-19, a more refined diagnosis of respiratory illness at the microbiological level is key to preventing pandemics. Covid-19 “wasn’t surprising, especially with what we saw in 2003 with coronaviruses emerging as a pandemic threat after the outbreak of SARS and then in 2012 with Middle East Respiratory Syndrome,” Adalja said. “So coronaviruses were on everybody’s radar.” [SARS came from civets, a wild cat, and MERS was an outbreak in Saudi Arabia that was spread by camels.]
The most immediate way to predict a pandemic, he said, is with deeper surveillance of symptoms that fit the coronavirus profile. “There are many types of conditions, including pneumonia, in which most doctors and most hospitals don’t diagnose down to the microbiological level,” he said. “There are many cases of viruses that have pandemic potential that are cluttered among all those cases of unexplained pneumonia and that are victims of a lack of diagnostic curiosity. If we have some idea of what is making people sick, the baseline pathogens, we’d be able to understand when something new is happening.”
Creating a world virus atlas has value, Adalja said. “I think it’s an important scientific endeavor to do the Global Virome Project and to catalogue viruses,” he said. “But it is not pandemic preparedness. A lot of those viruses you discover will not have the capacity to cause a pandemic.”
“We have only scratched the surface in terms of knowledge about the viruses that currently exist and are carried by animals.”
Tim Rieser, a senior foreign policy aide to Sen. Patrick Leahy (D-VT) who has worked on global health issues for 20 years, supports the concept of gathering a lot more information on the world’s viruses. Congress, he said, is now considering greatly increasing funding for such ventures.
“We have only scratched the surface in terms of knowledge about the viruses that currently exist and are carried by animals,” said Rieser. “The more we know about what’s out there, the better. It’s not a huge investment. We’re spending trillions of dollars to respond to Covid-19. If we invested a tiny fraction of that in prevention, capacity building, and data collection, we would be a lot better prepared to deal with it and the next deadly virus.”
Other approaches to pandemic prediction are being developed, including methods known as digital disease detection. ProMed and HealthMap, for example, use software that trawls the Internet, looking at online articles or Twitter feeds for the unusually frequent use of keywords — “fever” or “diarrhea” say — that could indicate an outbreak anywhere in the world. When these systems find these kinds of terms in abundance, they can alert experts.
But all the cutting-edge science won’t matter if policy makers don’t listen to scientists and have a plan in place. “You need a marriage between scientific discovery and political decision-making and policy formulation,” said Carroll.
Whatever the approach, in the wake of the Covid-19 outbreak a lot more attention will undoubtedly be focused on the problem. “We’ve invested billions of dollars to fight terrorism, but there is no terrorist who could achieve the harm this invisible microbe has,” said Rieser. “As bad as Covid-19 is, it could have been so much worse if it were as transmissible as this, but as deadly as Ebola.”