Viral outbreaks are on the rise. Ben Spencer meets the scientists racing to stop them becoming a global threat.
As the airlock swings shut, the safety co-ordinator issues a final reminder. “Please do not touch anything,” he says. Machines hum as we step into the containment lab. “This is where we work on some of the most dangerous viruses,” says Professor Tom Solomon, director of the Liverpool-based Pandemic Institute. “A lot of the initial Covid work was done here.”
Inside biological safety cabinets sit trays of purple cells infected with Japanese encephalitis virus — a mosquito-borne pathogen that can cause inflammation of the brain, paralysis and death. Solomon assures me the viruses being assessed today have been inactivated, meaning they can no longer infect humans, but the protocols here are still strict. Powerful fans suck any airborne microbes up into a filter, rather than being allowed to waft around the room. The most dangerous material is handled inside airtight cabinets using inbuilt rubber gauntlets. All other equipment can be used only with corresponding gloves, which are binned before anything else is touched.
“We need to be very careful,” repeats Felipe Cia Viciano, the safety man. I step away from the equipment. Inactivated or not the samples look pretty alarming. I don’t want inadvertently to cause a lab leak.
This Thursday marked three years since Boris Johnson ordered the UK into its first lockdown. Since then we have endured the biggest social and economic disruption since World War II. Some 219,000 people in the UK and nearly seven million globally have lost their lives to the virus. Solomon’s task is to ensure that never happens again. “If we wait for things to become pandemics then we’ve already failed in our mission,” he says.
The Pandemic Institute was founded in 2021 to monitor emerging diseases and prepare for future outbreaks. “Never again will we be unprepared” is its motto. It is not alone. Around the world, research institutes and universities are working on two key questions: where will the next pandemic come from? And how can we stop it?
Their investigations concern illnesses such as Ebola, Zika, Lassa fever and Nipah virus. These viruses and others like them form the bulk of the World Health Organisation’s list of “priority pathogens” — diseases that pose the greatest public health risk due to their “epidemic potential”. But most terrifying of all is the one at the very bottom of the list: Disease X.
This is the pathogen we don’t yet know about — a virus, bacterium or fungus that is yet to appear. It could be a mutated form of a disease we have lived with for years. Or a combination of animal viruses that evolve to jump into humans. Covid-19 was this era’s Disease X, emerging in Wuhan at the end of 2019 to change our world. What will be the next?
A dangerous blind spot
It is a subject few of us want to think about. And who can blame us? Covid is still with us, quietly taking 500 or so lives a week, but the dark days of March 2020 seem like a distant memory. We are able to forget thanks to the miracle of Covid vaccines. While the virus still kills some people, and long Covid blights many lives, our boosted immunity means that for most of us, infection will result in a relatively short illness.
The risk of forgetting history, however, is that we are destined to repeat it. Dame Kate Bingham, who chaired the vaccine taskforce at the height of the emergency, told a hearing of the Commons science and health committees in November that the UK’s pandemic preparedness had declined since the emergency ended. “Our approach seems to have been to go backwards rather than to continue the momentum,” she said.
Lord Bethell, who was a Conservative health minister in 2020 and 2021, agrees. “It’s in the psychology of all of us that we turn away from the bad things that have happened in our life. And that’s what’s happening,” he says. He is furious that testing infrastructure created from scratch during the pandemic has fallen out of use.
“For me, it’s totally heartbreaking. What you should do after a big pandemic is find other uses for that infrastructure. You turn the machines and the infrastructure to doing other public health screening. And then when the next pandemic turns up you have a platform to scale up from. But it has all been closed, the mega labs have been shut or sold. I think we will live to regret that.”
Sooner or later the next Disease X will appear. The course of human history has been punctuated by the emergence of such pathogens. The Black Death killed up to 200 million people in the 14th century. Russian flu, which scientists now believe was likely to have been caused by a coronavirus, swept across the world in the 1890s. Spanish flu took 50 million lives in the aftermath of World War I. And in the past four decades, HIV has killed 40 million people.
Modern science means we are now better equipped to battle these diseases, but they come along far more frequently thanks to growing human populations, intensive industrial farming and the illegal wildlife trade. Many experts believe the way we treat animals makes the “spillover” of pathogens to humans more likely. Deforestation and habitat loss has brought us in ever closer proximity to wildlife; huge wet markets in which live animals and fish are bought and sold provides an easy transmission route; vast farms — such as a 26-storey pig-breeding operation that opened last year in the Chinese province of Hubei — create mixing bowls for diseases.
Since the 1980s outbreaks of new diseases have tripled in number. And when they emerge they spread rapidly, flown around the globe by an increasingly mobile population. What once might have remained a localised outbreak can become a pandemic in a matter of weeks.
“It took a year for people to get around the planet 150 years ago,” Solomon says. “And the global population was 1.3 billion. Now it takes 24 hours to get around the world and there are eight billion of us, and we live in close proximity in megacities. We didn’t have intensive farming in the past.”
The leap from animals
Several times since the turn of the century we have been caught unawares by viruses that have either leapt from animals to humans for the first time or spread at an unprecedented pace: Sars-1, found in bats and palm civets as well as humans, appeared in China in 2002; H1N1 swine flu arrived in 2009; Mers jumped from camels to people in 2012, killing 36 per cent of those it infected; Ebola, which is thought to have originated in bats or primates, killed 11,300 people in 2014 and 2015; mosquito-borne Zika was reported in 86 countries in 2015 and 2016; and then there was Covid-19.
We will probably never know for sure whether the coronavirus jumped from bats or leaked in some disastrous accident from the Wuhan Institute of Virology. Scientists are divided on the matter, and while the FBI last month disclosed that it now believes a lab leak is the most likely explanation, other US agencies still think a zoonotic spillover was the probable cause.
We have to be on our guard for both possibilities in the future. As each of the epidemics that preceded Covid came and went, either seen off by science, the virus’s own weaknesses or by the laws of herd immunity, we became complacent. We have now, to all intents and purposes, seen off Covid too. But other threats remain — and they are growing.
Solomon points to Japanese encephalitis. First identified in humans in 1871, it is transmitted in a cycle between mosquitoes, pigs, waterbirds and people. The samples being analysed in the lab today were collected by Solomon in Vietnam in the 1990s. But now this virus is spreading through Australia for the first time, with 45 cases and seven deaths recorded so far. While vaccinations for Japanese encephalitis exist, inoculation is not routine in Australia. And once someone is infected there is no treatment. Most people experience no symptoms or something like mild flu, but if the infection spreads to the brain it kills one in three patients, and half of those who survive suffer permanent brain damage.
Solomon’s team is comparing the sequence of the Vietnamese samples with those taken in Australia to look for genetic changes. “You don’t need a crystal ball to realise that mosquito-borne pathogens are spreading,” he says. “Climate change means [mosquito habitat] range is expanding. In southern Europe we have mosquito-borne infections that we haven’t had previously.”
West Nile virus, which originated in Uganda, is another example. Like Japanese encephalitis it is spread when a mosquito bites an infected bird and then a person, which can cause a flu-like illness, muscle weakness and, in some cases, seizures. Until 1996 Europe had seen no significant outbreaks; last year there were 965 cases, most of them in Italy, with 73 deaths. The UK has not yet had any infections. But mosquito species that have the potential to carry West Nile virus or Japanese encephalitis have been found in the Kent marshes and even in the warm conditions of the London Underground.
Solomon reels off a list of other neglected threats: Nipah virus, which kills up to 75 per cent of those it infects; Marburg virus, a cousin of Ebola that has a fatality rate of 90 per cent; and superbugs, which he says will have a “massive” death toll if they evolve to evade the antibiotics at our disposal.
The bird flu threat
What is really keeping virologists up at night is H5N1 avian influenza — bird flu. “If there was an outbreak in humans tomorrow, we wouldn’t be able to vaccinate the world in 2023,” Jeremy Farrar, the outgoing director of the Wellcome Trust, said last month. “My concern is that we’re in slow motion watching something that may never happen, but if it were to happen we would look back and ask why we didn’t do more.”
The mortality rate of H5N1 is terrifying. Since it was first identified in Hong Kong in 1996 about 900 people have contracted it and 56 per cent have died. When Covid first emerged, by comparison, it killed 1.4 per cent of those it infected. Despite its high mortality rate, the threat of H5N1 to humanity is limited by the fact there is no evidence it has ever been transmitted from one human to another. In the parlance we all learned so quickly during the Covid pandemic, the R-rate of bird flu is 0. People are occasionally infected — usually because they keep ducks or work with poultry. But then they either recover or die. The virus — so far at least — has never been passed on.
In the past two decades waterbirds — particularly ducks, geese and wading birds — have been the main source of avian flu, bringing the virus with them as they flew into Britain each autumn from Europe and the Arctic. Occasionally it has spread to poultry, which had to be culled.
Last summer conservationists spotted something new. For the first time, the virus got into our seabird colonies. Gannets, guillemots, kittiwakes and puffins were found dead along the British coast. Ornithologists fear entire species could be wiped out in what is shaping up to be a conservation disaster. It is also a catastrophe for the poultry industry: the US alone has culled 50 million poultry and the UK at least four million. Countless millions of wild birds have died worldwide.
The jump of the virus to new avian species means it has found a new range, spreading deep into South America for the first time, with thousands of pelicans killed along the Peruvian coast. More worryingly, the virus has now been found in mammals such as sea lions in Peru, foxes and otters in Britain, and bears in North America. While most of these cases are thought to have been down to hunting or scavenging, mammal-to-mammal transmission has been confirmed on a mink farm in Spain.
“The outbreak in mink is a real warning sign,” says Professor Paul Digard, a virologist at the Roslin Institute at Edinburgh University. “I can’t think of a case before where we’ve seen this lineage of H5 transmitted between mammalian species outside of a laboratory setting.”
Experts stress that mink farms are a perfect breeding ground for infections, with thousands of the animals crammed together in captivity. To spread among mammals in other environments is a different prospect.
That was demonstrated in 2011 during experiments led by Ron Fouchier at the Erasmus University Rotterdam. The team genetically modified an H5N1 virus to see what changes were required to force it to transmit among ferrets. This “gain-of-function” study was controversial — critics argued that making a dangerous pathogen transmissible among humans was highly irresponsible. But the team made a significant discovery.
“They found entire constellations of mutations that were needed to get it to transmit between ferrets,” Digard says. “The odds of those changes happening by chance — when there’s no real benefit for the virus that’s living quite happily in birds — are small. There’s no real pressure to drive it through a multistep process.” But he adds: “Time and again with flu and other viruses, we work out ‘rules’ for how the virus behaves, and then we find a new variant that breaks those rules. H5N1 is absolutely the type of virus we need to worry about.”
Dr David Bauer, a virologist at the Francis Crick Institute in London, says there is another way bird flu can create problems for humans: a piece of virological trickery called reassortment. That is when two strains of influenza virus such as human flu and bird flu infect the same host and swap genetic information. “It acquires a new set of surface antigens. It changes its coat so it cannot be recognised and your immune system just has no idea what this thing is,” Bauer says. “It happened in 1957 and 1968 — the virus reached down into the avian reservoir and pulled out new segments. Those were particularly deadly years — there was complete escape of immunity.”
The swine flu pandemic of 2009 was caused by a “triple reassortment”. H1N1 in Mexico took genetic segments from both birds and pigs, spreading worldwide and killing up to half a million people.
Solomon agrees that pandemic influenza in general, and H5N1 in particular, is a significant risk. But he adds that in the past fears about flu have blinded politicians to other threats. “If all you’ve got in the dusty drawer is the flu pandemic preparedness plan, when a pandemic happens that’s what you pull out. Covid has taught us that we can’t just look at one pathogen. We need to look at a variety of threats.”
So where to start? With so many dangers to our health, how can scientists possibly identify a future Disease X and stop it before it spreads?
Meet the virus hunters
Gregory Gray, professor of infectious disease epidemiology at the University of Texas Medical Branch in Galveston, found one such threat in a fishing village at the mouth of the Rajang River in Sarawak, Malaysia. In 2017 a 5-month-old baby boy had become feverish and was struggling to breathe. He was taken to the nearest hospital, three hours away in the city of Sibu. There he was admitted to intensive care, where his lungs filled with mucus. He had pneumonia but doctors were puzzled as to what was causing it. The boy was discharged within a week, though he took several months to recover fully. A sample was sent to Gray’s lab in the US, along with 300 others from Sarawak.
Gray discovered the baby had been infected with a coronavirus found in dogs. Genetic sequencing suggested it had also exchanged parts of its genome with pigs and cats. Signs of this new dog-cat-pig coronavirus were identified in seven other patients in Sarawak. Strikingly, a similar virus has been identified in distant Haiti.
Gray believes that, while concerning, the virus is not an immediate threat. “What is often portrayed in movies is that these pathogens just jump over to humans and suddenly cause a pandemic,” he says. Instead, he believes animal viruses “spill over” into humans more often than we think. These viruses test the body, challenge its immune system and usually die off. Over time, however, they can evolve to colonise our cells, to replicate and to transmit between humans.
“Seventy per cent of new emerging threats detected in humans come from animals,” Gray says. He wants far more comprehensive surveillance of people sick with respiratory conditions and fevers, which he believes will detect more pathogens than are currently picked up.
It is a radical approach but if new diseases can be identified in this early phase — before they become transmissible — they can be stopped in their tracks.
He also wants to track farm workers, who are often the first to become infected. “If you work in close proximity with animals you are challenged,” he explains. “It is not a rare event.” His team has run trials among pig farmers in China, taking regular swabs and blood tests. They also took samples from the animals and tested the air and water. “It validated the idea that these farms are real mixing bowls for these viruses,” he says.
How to prevent a pandemic
Early surveillance is crucial if pandemics are to be averted. The Coalition for Epidemic Preparedness Innovations (Cepi), an Oslo-based international alliance of organisations, aims to stop emerging diseases 100 days after detection. Richard Hatchett, Cepi’s chief executive, says with better surveillance — and greater transparency — the world could have been alerted to Covid far earlier.
“Imagine if China had realised that they were dealing with a novel coronavirus in mid-December and started responding, rather than mid-January when they revealed it to the world,” he says. “Imagine if they had implemented efforts to control local transmission straight away.” That would have limited spread — potentially keeping the virus within Wuhan. “Then imagine if we could compress vaccine development timelines from the 11 months that we actually achieved from a cold start in 2020 down to 100 days. We would have been delivering vaccines in March.”
Instead of baking bread and learning how to use Zoom this time three years ago, we would have been queueing for jabs. Hatchett points out that in April 2020 just 2.2 million cases of Covid had been recorded globally. “In December, when the vaccines were available, there were 70 million cases.”
He extends his point further. If, by winding back the clock, Covid had been contained in Wuhan, and vaccines had been rapidly developed, then “you are talking about having vaccines available when there are 30,000 cases. Then you actually are working towards the possibility of preventing pandemics altogether.”
It is a tantalising thought. After all, lockdowns are a failure of public health policy, a last resort. But what would it take? Cepi has drawn up a US$3.5 billion ($5.6b) plan to kick-start the process, though it acknowledges more funding will be needed.
At its heart is the creation of a library of vaccines against a large proportion of the 250 viruses that we know can infect humans. Not every virus will need its own vaccine: the recent mpox (previously known as monkeypox) outbreak, which was tackled effectively outside of central and west Africa with established smallpox vaccines, has shown that existing jabs can be put to good use. But a seed bank of prototype vaccines against each of the 25 main viral families will be a start.
And it is doable. The “plug and play” vaccine technology that came to the fore to see off Covid has shown what can be achieved. The mRNA vaccines, as showcased by Pfizer-BioNTech and Moderna, and the adenovirus vector vaccines, developed by Oxford, are all programmable. Once the sequence of a virus is known, the jabs can be directed against a variety of threats.
This approach has its limitations. Most notably, after 40 years there are still no effective vaccines against HIV. If a similar retrovirus emerged, we would struggle to contain it. But Covid has shown us what is possible. Never before has the world vaccinated so many people as it did in 2021.
As Larry Brilliant, the American epidemiologist who helped eradicate smallpox, said in 2014: “Outbreaks are inevitable, but pandemics are optional.”
What did we learn from Covid?
Do facemasks work?
In March 2020 England’s deputy chief medical officer, Jenny Harries, advised the public that wearing face coverings was “not a good idea”. Doing so could “actually trap the virus in the mask”. By June there had been a u-turn. Masks were not only a good idea but we would be fined if we did not use them on public transport, in shops and health premises.
And now? The respected Cochrane Review recently concluded that masks “probably make little or no difference” to Covid outcomes. But this says more about the quality of the evidence than masks themselves. It is likely that face coverings reduce the risk of transmission to some degree — and other studies have found that N95-type respirators are far more effective than cloth coverings or surgical masks — but we still do not know by how much.
Antiviral hygiene
In the spring of 2020, hygiene advice went into overdrive. People started worrying whether parcels delivered to their homes might be contaminated with coronavirus. Clothing retailers were told to quarantine returned items for 48 hours. But scientists later concluded that inanimate objects were unlikely to play any meaningful role in the spread of Covid. While microscopic flecks of virus might linger on surfaces for a few days, there was little risk they could be transferred into someone’s lungs. Instead, the virus is spread in tiny aerosol droplets that can stay aloft for hours. Opening a window or two, rather than doing a deep clean, could make all the difference. Infected people spread viral particles when they talk, breathe, cough or sneeze. Social distancing works: exposure to such particles is reduced by between two and 10 times if people are 2m apart compared with 1m.
What about handwashing?
Handwashing is still advisable because of our inescapable habit of putting our hands to our face. The Cochrane Review found good hand hygiene cuts the risk of Covid and other acute respiratory infections by 14 per cent. It did not venture a conclusion on the impact of singing Happy Birthday while doing so.
Written by: Ben Spencer
© The Times of London