Finding the next pandemic virus before it finds us

Part of Pandemic-Proof, Future Perfect’s series on the upgrades we can make to prepare for the next pandemic.

Imagine if the world had a head start responding to SARS-CoV-2, the virus that causes Covid-19. What if the novel coronavirus weren’t so novel when it emerged in late 2019 because scientists had already studied and sequenced related viruses in the lab? What if it wasn’t shelved away, and medical researchers around the world had gained immediate access to virus samples and sequences, just days or weeks after it was first identified?

Those small gains would have had enormous consequences. The world might have ramped up testing more quickly, slowed the spread of the virus, and shaved months off the timeline for developing Covid-19 treatments and vaccines, potentially saving millions of lives. Or maybe scientists could have figured out the likeliest spots for a spillover and closed them off, perhaps preventing the pandemic altogether.

This is all hypothetical, but some scientists think it’s achievable. And they say we have an opportunity, right now, to avert some of the misery of a future pandemic.

We’ve had coronavirus outbreaks before, but they haven’t inspired the kind of sustained, large-scale, and collaborative science that could have prepared us for this one. After the SARS outbreak in 2003 and the MERS outbreak in 2012 — both of which were stopped by a combination of infection control methods and luck — research eventually tapered off. If it hadn’t, and scientists had continued seeking out, documenting, and sharing information about new potential threats, they might have found a direct ancestor to the SARS-CoV-2 virus. And perhaps treatments and vaccines would have been well underway as the first patients began to fall sick.

A pandemic like Covid-19 isn’t just a force of nature, nor is it a random event; human activity is increasing the chances of new diseases emerging. That fact presents a route toward countering a new outbreak before it begins, but it requires ramping up a two-pronged approach.

First, scientists need to narrow down the types of pathogens that are most worrisome and increase efforts to find them in potential hot spots. Then they need to construct a more comprehensive archive of infectious agents and share them for research in a safe way. Such a system could identify which viruses might trigger another pandemic as well as ramp up investigations into existing infectious diseases.

The fierce urgency of the global Covid-19 crisis illustrated the value of rapidly sharing information around viruses. The pandemic led to an extraordinary amount of collaboration among scientists, especially in the speed with which its genetic sequence was decoded and shared. There are now multiple international databases where researchers can upload their own sequence of the SARS-CoV-2 genome and compare it to millions of other strains. Those sequences accelerated research, helping deliver vaccines and treatments in record time. Surveillance of SARS-CoV-2 genomes also uncovered new variants of the virus, revealing their transmission routes and flagging concerning mutations.

“The sequence generation and the sharing that we’ve seen in the pandemic is really unprecedented,” said Emma Hodcroft, a molecular epidemiologist at the University of Bern. “We’ve never had a pathogen with this many sequences, ever.”

Developing a more comprehensive archive of viruses and their genomes will require countries to tackle thorny questions about governance, equity, transparency, and safety. It will also be expensive and time-consuming. But if it helps avert even a fraction of the gruesome human and economic toll of a future pandemic, it will be well worth it.

The tedious but necessary work of finding viruses with pandemic potential

For something so destructive, viruses are remarkably simple. At their core, they are just tiny fragments of genetic material — DNA or RNA — encased in a microscopic protein shell. They’re passive parasites that can’t reproduce without infecting a host. Many scientists don’t even consider them to be a form of life.

But that simplicity leads to an extraordinary variety of shapes, sizes, and victims. By one estimate, there are more individual viruses on Earth than there are stars in the universe. More than 320,000 different viruses infect mammals alone, and many more viruses infect fish, birds, reptiles, insects, plants, fungi, and bacteria.

The majority of new viruses in humans come from contact with animals. More than 200 virus species are known to infect humans, and scientists keep finding more pathogens with the potential to do so every year. Viruses are also prone to making mistakes as they make copies of themselves, so they mutate regularly. That’s why variants of SARS-CoV-2 — including the fast-spreading BA.2 omicron variant that now accounts for the majority of current global cases — keep turning up.

The sheer numbers mean it’s not practical to sample all the viruses in wildlife in the hope of finding the rare one capable of sickening people. Instead, scientists want to study the borderlands between humans and wildlife, where encroaching settlements and development are increasing the odds of a virus spilling over. Researchers can find viruses through active surveillance, where they seek out a group of animals or people to screen for infection, as well as through passive surveillance, where they test already sick animals or people for pathogens, or sample residues such as wastewater.

Stephen Goldstein, a virologist at the University of Utah, calls for “both active and passive surveillance of humans at animal/wildlife interfaces — farm workers, animal traders, retail vendors, etc., in areas that are hot spots for virus emergence.” That includes regions like the Amazon rainforest, where ongoing deforestation is forcing wildlife to move around and come into contact with people.

There are efforts underway by universities and research institutions in different countries to catalog these viruses, sampling the places where miners, ranchers, farmers, and property developers are encroaching on forests, grasslands, and deserts.

When researchers find a new virus, they examine its structure under a microscope. They also decode its genetic material, looking for specific markers that might indicate it’s capable of causing disease, or gathering a comprehensive sequence of its genome. Tracking changes in a virus’s genetic code creates a paper trail of where it may have come from and hint at where it might be going. From there, scientists sort the virus into categories and establish how it is related to other known specimens.

But finding a new virus is not enough. Since viruses are parasites, they need a host cell in order to reproduce — and they’re very picky about what they’ll infect. So researchers also need to build up a larger library of standardized cells, also known as cell lines, to study them in laboratories. Ideally, these cell lines should resemble as much as possible animal tissues that the virus infects in the wild.

However, there aren’t that many standardized cells that emulate some of the most common sources of disease. “Even though Ebola and MERS and SARS and now SARS-CoV-2, they all have a bat origin, we have [few] cell lines for bats,” said Gigi Gronvall, senior scholar at the Johns Hopkins Center for Health Security.

There are also risks to looking for new viruses. There is a chance that a virus hunter could be infected themselves, and in turn infect others, seeding a new outbreak. Identifying and sequencing new viruses that could potentially threaten humans could also create an “information hazard” as the ability to design new pathogens in a laboratory becomes easier and cheaper. That raises the risk that engineered viruses might escape in a lab accident or even be deliberately released. But more viruses will continue spilling over from animals into humans, regardless of whether anyone is tracking them. So it pays to pay attention.

Yet even two years into the Covid-19 pandemic, with so much of the world’s attention on it, there are still yawning gaps in surveillance for the virus behind it. And there are even fewer efforts to shine a light on other pathogens lurking in the shadows. The World Health Organization recently reported that one-third of countries still don’t have adequate capacity to identify, sequence, and share the genomes of pathogens generally.

“I am concerned about this kind of ‘if we don’t look for them, they can’t hurt us’ philosophy,” said Gronvall.

Who controls virus research?

After identifying a new virus, the next critical step is to share the information. The Covid-19 pandemic has vividly demonstrated the benefits of researchers and countries working together effectively, as well as the perils when they fail to do so.

The SARS-CoV-2 virus that causes Covid-19 was first isolated in December 2019 and scientists in China made its genome sequence publicly available, paving the way for historically rapid development and distribution of vaccines and targeted treatments like monoclonal antibodies and antiviral drugs.

But genetic sequences alone aren’t sufficient. “We’re not yet good enough, certainly with coronaviruses, to be able to look at a sequence and have a good sense of whether or not it’s going to affect people in a real way,” Gronvall said. Researchers also need to work with live viruses too.

The need to experiment on live viruses poses some challenges for scientists trying to work across borders. SARS-CoV-2 has spread to just about every country in the world, temporarily mooting many of the international rules governing how viruses can be shared. But preventing or even blunting a pandemic requires acting before it has spread globally, and at that stage, such regulations — which weren’t designed for a public health emergency — could be an obstacle.

“Pathogens, even though they can go around the world easily, are under the sovereign rights of countries in which they are found,” said Amber Hartman Scholz, head of science policy at Leibniz Institute DSMZ German Collection of Microorganisms and Cell Cultures. “That law is underneath the Convention on Biological Diversity and promulgated through the Nagoya Protocol.”

The Convention on Biological Diversity is an international treaty — albeit one notably not ratified by the United States — governing how countries preserve nature, within and across borders. The Nagoya Protocol focuses on “genetic resources” and sets guidelines to ensure that countries where these resources are found get a slice of future benefits. If a virus is found within the borders of a given country, for instance, it should get easy access to the drugs or vaccines that target the pathogen. The country could also claim a portion of the profits generated by those pharmaceuticals.

Concerns about how benefits will be shared have hampered responses to diseases before. In 2007, Indonesia declined to send samples of the H5N1 influenza virus to the World Health Organization for vaccine development. Indonesian health officials said they were left out of important research on influenza in the past and weren’t able to afford the resulting vaccines. They worried that if Indonesia discovered a true pandemic virus, the country would again struggle to buy the tools to protect its people.

“Countries that are hardest hit by a disease must also bear the burden of the cost for vaccine, therapeutics and other products, while the monetary and non-monetary benefits of these products go to the manufacturers that are mostly in the industrialised countries,” Indonesian health officials wrote in a 2008 paper explaining their rationale.

If a new virus emerges, bureaucratic wrangling between governments could stall progress at the critical stages when prevention is still a possibility. And without resolving equity concerns, people on the front lines of the outbreak might not see any upside for sharing their findings, which in turn could delay the development of vaccines and antivirals needed to protect the entire world.

“It’s completely unclear under what legal conditions they’re there and whether or not they can actually be legally shared downstream and who, what, when, where, and why should benefit from them,” Scholz said.

There are more tools than ever, but virus research needs to reward transparency

The World Health Organization is working to resolve some of the policy hurdles with a pandemic treaty to help encourage sharing information and resources, though the exact provisions are still under negotiation. Some researchers have also proposed creating a Global Virome Project to coordinate international efforts to find and sequence genomes of viruses. Free websites like GISAID and Nextstrain collect viral genome information and provide tools for analyzing them. For live viruses, groups like the American Type Culture Collection and the European Virus Archive store virus samples and share them with laboratories around the world to conduct experiments.

These “biobanks,” usually nonprofits or government institutions, have helped streamline research on viruses, expanding it from an ad hoc club of labs around the world. That has made virus research more accessible to places with fewer resources and more visible for public scrutiny. “There are some common principles in biobanks. One of them is transparency,” said Christine Prat, business developer at the European Virus Archive. “The other is impartiality.”

Researchers around the world can then receive virus samples from biobanks (usually only at the cost of shipping), provided they meet safety and security requirements. Some governments, like that of the US, also have rules restricting pathogens that might be repurposed as bioweapons.

Right now, though, there are dozens of research labs for dangerous viruses around the world, but most of them don’t meet the highest standards of safety, transparency, and information-sharing. That raises the slippery question of how best to share virus samples and sequences if everyone isn’t meeting the same benchmarks.

And looking for a dangerous virus isn’t a guarantee that a threat will be found in time, nor that politics won’t interfere with the effort. Writing in Vanity Fair, journalist Katherine Eban last week noted that there indeed was a group, EcoHealth Alliance, that received $3.7 million from the US National Institutes of Health in 2014 to screen bats in China for coronaviruses, but did not anticipate SARS-CoV-2.

Eban also highlighted a preprint paper posted last year by Jesse Bloom, a professor at the Fred Hutchinson Cancer Research Center. He found that early sequences of SARS-CoV-2 were deleted from an NIH database and concluded the agency did so at the behest of researchers in China for unclear reasons. The sequences have since been reposted online.

In addition, finding and documenting a new virus won’t be enough to stop another pandemic unless policymakers and scientists recognize it as a threat and start to take action. They also have to create a culture that encourages and rewards sharing these discoveries.

The Wuhan Institute of Virology, for instance, had documented a coronavirus in 2013 that caused illnesses among a group of miners. When they compared it to SARS-CoV-2 in 2020, they found their genomes had 96 percent overlap. The presence of this earlier virus, known as RaTG13, fueled theories that SARS-CoV-2 leaked from the lab. However, other virologists looking at the family tree of both viruses concluded they came from different branches and that SARS-CoV-2 didn’t descend from RaTG13. No direct predecessor of SARS-CoV-2 has been found at the Wuhan Institute of Virology, nor has one been found in the wild, leaving definitive answers about its origins murky.

Scientists did find evidence that the virus likely spilled over more than once into humans at a live animal market in Wuhan. Environmental samples showed that the earliest traces of SARS-CoV-2 clustered around a specific animal seller in the market. The findings, published in pre-print papers in February, point toward a natural origin of the disease.

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But the Chinese government’s behavior has worsened suspicions. Health officials around the world criticized China for withholding crucial information about the origins of Covid-19. The US government has also said China downplayed the severity of Covid-19 in the early days of the pandemic. The Wuhan Institute of Virology took down its virus database in September 2019. Lab officials said this was a precaution due to cyberattacks, though researchers around the world have asked them to bring it back online. Chinese researchers also have to get government approval to publish research on Covid-19.

So while China may have documented a relative of SARS-CoV-2 years ago, they did little with the information on their own and didn’t share it during critical stages of the Covid-19 pandemic.

On the flip side, South Africa discovered and documented some of the first cases of the omicron variant of SARS-CoV-2 in 2021. But the disclosure led to travel bans that hurt the country’s economy while doing virtually nothing to prevent omicron from spreading around the world.

“It’s not hard to imagine other countries look at this and say, ‘We don’t want to find a variant,’” Hodcroft said.

We can get started now and begin reaping the benefits right away

It’s not clear when the Covid-19 crisis will finally fade away, but it will eventually, and researchers say some of the attention could be refocused onto other diseases with great effect. Even efforts to counter non-pandemic viruses like HIV could see major advances if scientists had a better understanding of the changes taking place.

“The odds of us correctly predicting what will be the next pandemic virus … are probably not in our favor, but the more we understand about all virus strains, the better position we’ll be in,” Hodcroft said. “If we took all the sequencing that’s being done for SARS-CoV-2 and just spread that to the three or four next common viruses, we would absolutely blow our minds with how much we would add to our knowledge of those viruses.”

Mapping out the ominous viruses lurking at the reaches of human civilization will also take time, and countries will likely spend years hammering out rules to govern how they find and share research around disease. Given the perpetual risk of a new virus emerging, the world needs to act now.

“In 20 years, I want to look back on this and say, ‘Wow, we are in a so much better position to know what is going to be dangerous,’” Gronvall said. “Some of these research questions will take time, and there’s no time like the present to start working on them.”

Source: https://www.vox.com/22945860/covid-19-virus-pandemic-surveillance-sequence