LURKING in the air, water, soil and inside every other living creature, viruses have us surrounded and hopelessly outnumbered. For every star in the known universe, there are at least . They are so small that more than 100 million .
As 2020 has shown, just one of these is enough to bring society to its knees. The covid-19 pandemic offers a grim demonstration of how hard it can be to stop a new infection once it takes hold in the human population.
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But what if we could hunt down the next pandemic-causing virus before it starts spreading? If surveillance of viruses evolving in animals could identify the likely candidates, then we might be able to pinpoint the all-important leap they could make into humans. And by identifying the animal species carrying the most problematic viruses, measures could be put in place to prevent their spread.
This kind of viral detective hunt is a Herculean endeavour, even before you add the difficulty of predicting which candidate out of millions will go on to infect us. Critics argue that it is impossible to stop the occasional rogue virus from jumping into humans and that we should instead focus on stamping out those infections when they occur. The debate has split scientists, but it needs to be resolved soon. Even as we continue to battle covid-19, the clock is ticking down towards the next outbreak of a novel pathogen.
The health of humans, wildlife and ecosystems is intimately connected. As our population grows, more people live in contact with wild and domestic animals and so the odds rise that “zoonotic” pathogens will spill over species barriers to infect us.
Yet even if new viral pandemics that spread from animals are inevitable, they are also staggeringly unlikely events. Fate and biology must combine in a precise way to put the wrong virus in the wrong place at the wrong time. First, a virus circulating in an animal must pose a threat to humans. Most don’t. They lack one or more of the bits of molecular machinery needed to bind onto human cells, replicate once inside and then spread further to other cells and other people – all without being mopped up by the immune system. Next, the animal harbouring a potentially dangerous virus has to come into contact with a susceptible person and shed enough infectious material near them to pose a threat. Lastly, the person needs to be infected by the virus somehow and be in sufficient contact with others to spread it.
Breaking barriers
Thankfully, this series of hurdles is so difficult for a virus to clear that, of the millions of different types of viruses believed to be out there, . Unfortunately, however, some of the natural barriers that protect us from the viral threat are eroding and others have been smashed to bits. International air travel means that few outbreaks can be contained as local problems. A virus can now travel across the world in less than a day, giving medics and scientists little time to react – hence the call for better surveillance to act as an early-warning system.
“We absolutely need to understand what viruses are circulating in animals,” says Tracey Goldstein, a specialist in viral surveillance at the University of California, Davis. “We need to understand more about the hosts and their behaviour and when they might be shedding the viruses.”
At its most ambitious, such a surveillance scheme would sample and sequence the genomes of the viruses that live within all wild and domestic animals that humans could encounter. That’s a lot of animals, but an even larger number of viruses. Nobody knows for sure how many viruses such an effort would need to find and analyse, but it is . That is likely to cost a few billion dollars and entail a decade of trudging around caves, jungles and forests looking for species and taking samples of their urine, saliva and droppings.
“Fate and biology combine to put the virus in the wrong place at the wrong time”
Such a scheme was proposed in 2016. The is marketed as “the beginning of the end of the pandemic era”. Although it can boast some high-profile supporters – former UK prime minister David Cameron – it is yet to raise the necessary funds.
This project isn’t the only attempt at global surveillance, and it isn’t the only initiative to illustrate the scale of the undertaking. A US government-funded programme called was launched in 2009 to provide an early warning of pandemics, prompted by the 2005 bird flu outbreak. PREDICT was ). Spending $207 million in 60 countries and taking 164,000 samples from wildlife, livestock and humans, it discovered 949 novel viruses. In other words, PREDICT only scratched the surface of an estimated 10,000 potentially zoonotic viruses in wild mammals. It found just one that was possibly linked to deaths in humans – the – and it didn’t spot the coronavirus that causes covid-19.
1.6 million
Estimated
“We targeted the animals that we thought had the highest potential to carry the most viruses that could spill over,” says Goldstein, one of the leaders of PREDICT. “That’s not completely comprehensive, but you have to start somewhere. And we targeted primarily RNA viruses. Those are the ones that are less stable and those are the ones that have caused most of the pandemics in the past.”
Finding a virus in an animal is just the start. The next step is to assess the potential pandemic risk by seeing if it can infect human cells in lab tests. Most viruses from animals can’t do this because they lack the proteins needed to bind to our cell receptors. For example, the PREDICT team found a coronavirus in a bat in Uganda in 2017 that looked genetically similar to the MERS virus, which is found in camels and can infect people. But there were , which viruses use to penetrate would-be host cells. Lab tests confirmed that this made it harmless to humans.
In 2013, the team identified a . It could infect human cells, but there was no evidence it had actually infected people. And in 2018, the project identified another novel virus in a bat, this time in Sierra Leone. Called , it is from the same family as Ebola. Lab experiments confirmed that it could infect human cells, yet, again, there is no evidence that anyone has actually caught it or that it could be spread from person to person. It isn’t even clear whether the Bas-Congo virus is a human pathogen. It was found in blood samples taken from a nurse who treated two children who died of a haemorrhagic fever in the Democratic Republic of the Congo in 2009. But the virus hasn’t been found in anybody else since, and something else could have killed the children.
Another programme to detect emerging viral threats took place in Vietnam, and focused on people who live and work closely with animals at high risk for zoonotic pathogen transfer. From 2013 to 2016, the followed almost 600 farmers, animal-health workers and people involved with animal slaughter or who . Whenever one of them reported a cough, sore throat or fever, local doctors would visit within 48 hours to take samples and record details about their exposure to animals.
About two-thirds of the workers developed a respiratory infection over the three-year period. found mostly common pathogens such as the influenza A virus, but also some novel viruses. It isn’t clear where these came from or if they might pose a clinical risk, but the VIZIONS researchers say their discovery proves that this type of screening is an effective way to catch emerging zoonotic infections.
Even when viruses do get inside host cells, they still face the challenge of replicating without alerting the immune system. And we don’t fully understand what changes allow a virus to flourish in one species and struggle in another.
500,000
Estimated
A successful zoonotic virus – including SARS-CoV-2, the cause of covid-19 – tends to be a generalist, says Mike Farzan, an immunologist at Scripps Research in Florida. . Zoonotic pathogens with many different host species have a higher chance of survival, and of eventually finding their way into the human population. As well as bats, SARS-CoV-2 has been found to infect a wide ranage of animals including pet cats and dogs, lions and tigers at a New York zoo, farmed mink and wild ferrets, hamsters and macaques – although the risk of a person catching covid-19 from these animals is believed to be low. So viruses that can spread from animal to animal are a priority for scientists looking for potential human threats.
Take Hendra virus, which is usually found in bats but can be passed to horses, and from them into people, causing fever, coughs and sometimes meningitis and coma. Dozens of outbreaks and four deaths have been reported in north-eastern Australia since 1994. Hendra outbreaks are linked to periods of heavy rainfall, says Raina Plowright, an infectious disease ecologist at Montana State University. In wet conditions, trees such as the eucalyptus produce fewer flowers for infected bats to eat. As a result, they are more likely to search for food on farms, where they may come into contact with horses. Hungry bats are also stressed and so tend to shed higher quantities of the virus.
Understanding this transmission cycle could allow scientists to better predict outbreaks, from studying weather cycles perhaps, or checking on viral levels in the bats. It also suggests a possible way to stop spillover events from happening. “A postdoc in my lab a few years ago suggested we set up mango juice stands for the bats and I remember laughing,” says Plowright. “But we’ve come to realise that’s the killer experiment. We’re starting to build up a nice evidence base that replanting winter-flowering trees could stop spillover.”
A similar approach is being used to stop the Nipah virus being passed from bats to humans in South-East Asia. The virus causes flu-like symptoms and brain inflammation and is often fatal, but its spread can be curtailed by using nets to prevent bats , a popular drink in the region.
Pandemic prediction
The ecosystem approach could combat viral threats identified elsewhere too, but it requires serious investment to understand complex ecological scenarios, viral dynamics and the interplay of wild and domestic species. “There needs to be a push to galvanise activities in a coordinated, globally funded way,” says Barbara Han at the Cary Institute of Ecosystem Studies in New York. “In order to do pandemic prediction or prevention with any level of accuracy, you have to have a way of assessing the who, what, where, when and why of spillover. And ecology is really critical for getting at all of those areas.”
The research needed to fill the gaps in knowledge sounds old-fashioned in an age of genome sequencing. It comprises basic questions related to things like social structures and the interactions of animal groups, their metabolism, lifespan and how many times a year they have offspring. “These things might seem a bit removed from our goal of being able to predict pandemics, but if you don’t know what the animals are doing, then you’re not going to have a chance of being able to make predictions that are useful,” says Han.
Not everyone agrees. Colin Carlson, a biologist at Georgetown University in Washington DC, says the idea that basic ecological studies can prevent pandemics is an example of the unhelpful “covidisation” of research. The risk, he says, is that attention and funds get diverted away from proven methods of fighting infections and protecting public health. Hype over the importance of viral surveillance means “you have a bunch of wildlife biologists essentially at the forefront of global efforts to prevent the next pandemic”.
$1.2 billion
surveillance programme
A similarly damning argument was made in an by three leading biologists, who argued that efforts such as PREDICT and the Global Virome Project were of little practical value and that “making promises about disease prevention and control that cannot be kept will only further undermine trust”. Money should be spent instead on boosting health capacity in developing countries, to spot the early signs of infection in people, they argued.
But Jonathan Epstein, a disease ecologist with the EcoHealth Alliance, a conservation and public health organisation that was part of the PREDICT programme, insists that viral surveillance offers a way to slash the risk of spillover events – even if it can’t always stop them. Changing human behaviour to keep people away from the sources of zoonotic viruses in the first place is key, he says, using methods such as tighter controls on live animal markets.
“You can certainly understand what the major activities are that promote spillover and work to reduce the risk there,” he says. “We have to try to reduce risks but at the same time be ready to respond when an outbreak does happen.”
949
by the PREDICT surveillance programme
Most of the world got that response wrong this time around – too slow, too little and too late. We didn’t heed earlier warnings. This is a planet of viruses, and we need to take the fight to them.
